protein

[French protéine, from Late Greek prōteios, of the first quality, from Greek prōtos, first.]

For more information on protein, visit Britannica.com.

Concept

Most of us recognize the term protein in a nutritional context as referring to a class of foods that includes meats, dairy products, eggs, and other items. Certainly, proteins are an important part of nutrition, and obtaining complete proteins in one's diet is essential to the proper functioning of the body. But the significance of proteins extends far beyond the dining table. Vast molecules built from enormous chains of amino acids, proteins are essential building blocks for living systems—hence their name, drawn from the Greek proteios, or "holding first place." Proteins are integral to the formation of DNA, a molecule that contains genetic codes for inheritance, and of hormones. Most of the dry weight of the human body and the bodies of other animals is made of protein, as is a vast range of things with which we come into contact on a daily basis. In addition, a special type of protein called an enzyme has still more applications.

How It Works

The Complexities of Biochemistry

Protein is a foundational material in the structure of most living things, and as such it is rather like concrete or steel. Just as concrete is a mixture of other ingredients and steel is an alloy of iron and carbon, proteins, too, are made of something more basic: amino acids. These are organic compounds made of carbon, hydrogen, oxygen, nitrogen, and (in some cases) sulfur bonded in characteristic formations.

Amino acids are discussed in more depth within the essay devoted to that topic, though, as noted in that essay, it is impossible to treat such a subject thoroughly without going into an extraordinarily lengthy and technical discussion. Such is the case with many topics in biochemistry, the area of the biological sciences concerned with the chemical substances and processes in organisms: the deeper within the structure of things one goes, and the smaller the items under investigation, the more complex are the properties and interactions.

The Basics

Amino acids react with each other to form a bond, called a peptide linkage, between the carboxyl group of one amino acid (symbolized as-COOH) and the amino group (-NH₂) of a second amino acid. In this way they can make large, chainlike molecules called polymers, which may contain as few as two or as many as 3,000 amino-acid units. If there are more than 10 units in a chain, the chain is called a polypeptide, while a chain with 50 or more amino-acid units is known as a protein.

All the millions of different proteins in living things are formed by the bonding of only 20 amino acids into long polymer chains. Because each amino acid can be used many times along the chain, and because there are no restrictions on the length of the chain, the number of possible combinations for the creation of proteins is truly enormous: about two quadrillion, or 2,000,000,000,000,000. Just as not all sequences of letters make sense, however, not all sequences of amino acids produce functioning proteins. In fact, the number of proteins that have significance in the functioning of nature is closer to about 100,000. This number is considerably smaller than two quadrillion—about 1/2,000,000,000th of that larger number, in fact—but it is still a very large number.

Components Other Than Amino Acids

The specific properties of each kind of protein are largely dependent on the kind and sequence of the amino acids in it, yet many proteins include components other than amino acids. For example, some may have sugar molecules (sugars are discussed in the essay on Carbohydrates) chemically attached. Exactly which types of sugars are attached and where on the protein chain attachment occurs vary with the specific protein. Other proteins may have lipid, or fat, molecules chemically bonded to them. Sugar and lipid molecules always are added when synthesis of the protein's amino-acid chain is complete. Many other types of substance, including metals, also may be associated with proteins; for instance, hemoglobin, a pigment in red blood cells that is responsible for transporting oxygen to the tissues and removing carbon dioxide from them, is a protein that contains an iron atom.

Structures and Synthesis

Protein structures generally are described at four levels: primary, secondary, tertiary, and quaternary. Primary structure is simply the two-dimensional linear sequence of amino acids in the peptide chain. Secondary and tertiary structures both refer to the three-dimensional shape into which a protein chain folds. The distinction between the two is partly historical: secondary structures are those that were first discerned by scientists of the 1950s, using the techniques and knowledge available then, whereas an awareness of tertiary structure emerged only later. Finally, quaternary structure indicates the way in which many protein chains associate with one another. For example, hemoglobin consists of four protein chains (spirals, actually) of two slightly different types, all attached to an iron atom.

Protein synthesis is the process whereby proteins are produced, or synthesized, in living things according to "directions" given by DNA (deoxyribonucleic acid) and carried out by RNA (ribonucleic acid) and other proteins. As suggested earlier, this is an extraordinarily complex process that we do not attempt to discuss here. Following synthesis, proteins fold up into an essentially compact three-dimensional shape, which is their tertiary structure.

The steps involved in folding and the shape that finally results are determined by such chemical properties as hydrogen bonds, electrical attraction between positively and negatively charged side chains, and the interaction between polar and nonpolar molecules. Non Polar molecules are called hydrophobic, or "water-fearing," because they do not mix with water but instead mix with oils and other substances in which the electric charges are more or less evenly distributed on the molecule. Polar molecules, on the other hand, are termed hydrophilic, or "water-loving," and mix with water and water-based substances in which the opposing electric charges occupy separate sides, or ends, of the molecule. Typically, hydrophobic amino-acid side chains tend to be on the interior of a protein, while hydrophilic ones appear on the exterior.

Real-Life Applications

Proteins Are Everywhere

Although it is very difficult to discuss the functions of proteins in simple terms, and it is similarly challenging to explain exactly how they function in everyday life, it is not hard at all to name quite a few areas in which these highly important compounds are applied. As we noted earlier, much of our bodies' dry weight—that is, the weight other than water, which accounts for a large percentage of the total—is protein. Our bones, for instance, are about one-fourth protein, and protein makes up a very high percentage of the material in our organs (including the skin), glands, and bodily fluids.

Humans are certainly not the only organisms composed largely of protein: the entire animal world, including the animals we eat and the microbes that enter our bodies (see Digestion and Parasites and Parasitology) likewise is constituted largely of protein. In addition, a whole host of animal products, including leather and wool, are nearly pure protein. So, too, are other, less widely used animal products, such as hormones for the treatment of certain conditions—for example, insulin, which keeps people with diabetes alive and which usually is harvested from the bodies of mammals.

Proteins allow cells to detect and react to hormones and toxins in their surroundings, and as the chief ingredient in antibodies, which help us resist infection, they play a part in protecting our bodies against foreign invaders. The lack of specific proteins in the brain may be linked to such mysterious, terrifying conditions as Alzheimer and Creutzfeldt-Jakob diseases (discussed in Disease). Found in every cell and tissue and composing the bulk of our bodies' structure, proteins are everywhere, promoting growth and repairing bone, muscles, tissues, blood, and organs.

Enzymes

One particularly important type of protein is an enzyme, discussed in the essay on that topic. Enzymes make possible a host of bodily processes, in part by serving as catalysts, or substances that speed up a chemical reaction without actually participating in, or being consumed by, that reaction. Enzymes enable complex, life-sustaining reactions in the human body—reactions that would be too slow at ordinary body temperatures—and they manage to do so without forcing the body to undergo harmful increases in temperature. They also are involved in fermentation, a process with applications in areas ranging from baking bread to reducing the toxic content of wastewater. (For much more on these subjects, see Enzymes.)

Inside the body, enzymes and other proteins have roles in digesting foods and turning the nutrients in them—including proteins—into energy. They also move molecules around within our cells to serve an array of needs and allow healthful substances, such as oxygen, to pass through cell membranes while keeping harmful ones out. Proteins in the chemical known as chlorophyll facilitate an exceptionally important natural process, photosynthesis, discussed briefly in Carbohydrates.

Proteins, Blood, and Crime

The four blood types (A, B, AB, and O) are differentiated on the basis of the proteins present in each. This is only one of many key roles that proteins play where blood is concerned. If certain proteins are missing, or if the wrong proteins are present, blood will fail to clot properly, and cuts will refuse to heal. For sufferers of the condition known as hemophilia, caused by a lack of the proteins needed for clotting, a simple cut can be fatal.

Similarly, proteins play a critical role in forensic science, or the application of medical and biological knowledge to criminal investigations. Fingerprints are an expression of our DNA, which is linked closely with the operation of proteins in our bodies. The presence of DNA in bodily fluids, such as blood, semen, sweat, and saliva, makes it possible to determine the identity of the individual who perpetrated a crime or of others who were present at the scene. In addition, a chemical known as luminol assists police in the investigation of possible crime scenes. If blood has ever been shed in a particular area, such as on a carpet, no matter how carefully the perpetrators try to conceal or eradicate the stain, it can be detected. The key is luminol, which reacts to hemoglobin in the blood, making it visible to investigators. This chemical, developed during the 1980s, has been used to put many a killer behind bars.

Designer Proteins

These are just a very few of the many applications of proteins, including a very familiar one, discussed in more depth at the conclusion of this essay: nutrition. Given the importance and complexity of proteins, it might be hard to imagine that they can be produced artificially, but, in fact, such production is taking place at the cutting edge of biochemistry today, in the field of "designer proteins."

Many such designs involve making small changes in already existing proteins: for example, by changing three amino acids in an enzyme often used to improve detergents' cleaning power, commercial biochemists have doubled the enzyme's stability in wash water. Medical applications of designer proteins seem especially promising. For instance, we might one day cure cancer by combining portions of one protein that recognizes cancer with part of another protein that attacks it. One of the challenges facing such a development, however, is the problem of designing a protein that attacks only cancer cells and not healthy ones.

In the long term, scientists hope to design proteins from scratch. This is extremely difficult today and will remain so until researchers better understand the rules that govern tertiary structure. Nevertheless, scientists already have designed a few small proteins whose stability or instability has enhanced our understanding of those rules. Building on these successes, scientists hope that one day they may be able to design proteins to meet a host of medical and industrial needs.

Proteins in the Diet

Proteins are one of the basic nutrients, along with carbohydrates, lipids, vitamins, and minerals (see Nutrients and Nutrition). They can be broken down and used as a source of emergency energy if carbohydrates or fats cannot meet immediate needs. The body does not use protein from food directly: after ingestion, enzymes in the digestive system break protein into smaller peptide chains and eventually into separate amino acids. These smaller constituents then go into the bloodstream, from whence they are transported to the cells. The cells incorporate the amino acids and begin building proteins from them.

Animal and Vegetable Proteins

The protein content in plants is very small, since plants are made largely of cellulose, a type of carbohydrate (see Carbohydrates for more on this subject); this is one reason why herbivorous animals must eat enormous quantities of plants to meet their dietary requirements. Humans, on the other hand, are omnivores (unless they choose to be vegetarians) and are able to assimilate proteins in abundant quantities by eating the bodies of plant-eating animals, such as cows. In contrast to plants, animal bodies (as previously noted) are composed largely of proteins. When people think of protein in the diet, some of the foods that first come to mind are those derived from animals: either meat or such animal products as milk, cheese, butter, and eggs. A secondary group of foods that might appear on the average person's list of proteins include peas, beans, lentils, nuts, and cereal grains.

There is a reason why the "protein team" has a clearly defined "first string" and "second string." The human body is capable of manufacturing 12 of the 20 amino acids it needs, but it must obtain the other eight—known as essential amino acids—from the diet. Most forms of animal protein, except for gelatin (made from animal bones), contain the essential amino acids, but plant proteins do not. Thus, the nonmeat varieties of protein are incomplete, and a vegetarian who does not supplement his or her diet might be in danger of not obtaining all the necessary amino acids.

For a person who eats meat, it would be extremely difficult not to get enough protein. According to the U.S. Food and Drug Administration (FDA), protein should account for 10% of total calories in the diet, and since protein contains 4 calories per 0.035 oz. (1 g), that would be about 1.76 oz. (50 g) in a diet consisting of 2,000 calories a day. A pound (0.454 kg) of steak or pork supplies about twice this much, and though very few people sit down to a meal and eat a pound of meat, it is easy to see how a meat eater would consume enough protein in a day.

For a vegetarian, meeting the protein needs may be a bit more tricky, but it can be done. By combining legumes or beans and grains, it is possible to obtain a complete protein: hence, the longstanding popularity, with meat eaters as well as vegetarians, of such combinations as beans and rice or peas and cornbread. Other excellent vegetarian combos include black beans and corn, for a Latin American touch, or the eastern Asian combination of rice and tofu, protein derived from soybeans.

Where to Learn More

"DNA and Protein Synthesis." John Jay College of Criminal Justice, City University of New York (Web site). <http://web.jjay.cuny.edu/~acarpi/NSC/12-dna.htm>.

Inglis, Jane. Proteins. Minneapolis, MN: Carolrhoda Books, 1993.

Kiple, Kenneth F., and Kriemhild Coneé Ornelas. The Cambridge World History of Food. New York: Cambridge University Press, 2000.

"Proteins and Protein Foods." Food Resource, Oregon State University (Web site). <http://www.orst.edu/food-resource/protein/>.

Silverstein, Alvin, Virginia B. Silverstein, and Robert A. Silverstein. Proteins. Brookfield, CT: Millbrook Press, 1992.

Structural Classification of Proteins (Web site). <http://scop.mrc-lmb.cam.ac.uk/scop/>.

THINK: Teenage Health Interactive Network (Web site). <http://library.thinkquest.org/29500/nutrition/nutrition.fap.shtml>.

A biological macromolecule made up of various α-amino acids that are joined by peptide bonds. A peptide bond is an amide bond formed by the reaction of an α-amino group (NH₂) of one amino acid with the carboxyl group (COOH) of another, as shown below. Proteins generally contain from 50 to 1000 amino acid residues per polypeptide chain.

Occurrence

Proteins are of importance in all biological systems, playing a wide variety of structural and functional roles. They form the primary organic basis of structures such as hair, tendons, muscle, skin, and cartilage. All of the enzymes, the catalysts in biochemical transformations, are protein in nature. Many hormones, such as insulin and growth hormone, are proteins. The substances responsible for oxygen and electron transport (hemoglobin and the cytochromes, respectively) are conjugated proteins that contain a metalloporphyrin as the prosthetic group. Chromosomes are highly complex nucleoproteins, that is, proteins conjugated with nucleic acid. Viruses are also nucleoprotein in nature. Of the more than 200 amino acids that have been discovered either in the free state or in small peptides, only 20 amino acids are present in mammalian proteins. Thus, proteins play a fundamental role in the processes of life. See also Amino acids.

Specificity

The linear arrangement of the amino acid residues in a protein is termed its sequence (primary structure). The sequence in which the different amino acids are linked in any given protein is highly specific and characteristic for that particular protein.

This specificity of sequence is one of the most remarkable aspects of protein chemistry. The number of possible permutations of sequence in even so small a protein as insulin, of molecular weight 5732 and with 51 amino acid residues, is astronomic: 1051 permutations. Yet it has been established that the pancreatic cell of a given species has only one of these possible sequences. The elucidation of the mechanism conferring such a high degree of specificity on the biosynthetic reactions by which proteins are built up from free amino acids has been one of the key problems of modern biochemistry.

Proteins are not stretched polymers; rather, the polypeptide backbone of the molecule can fold in several ways by means of hydrogen bonds between the carbonyl oxygen and the amide nitrogen. The folding of each protein is determined by its particular sequence of amino acids. The long polypeptide chains of proteins, particularly those of the fibrous proteins, are held together in a rather well-defined configuration. The backbone is coiled in a regular fashion, forming an extended helix. As a result of this coiling, peptide bonds separated from one another by several amino acid residues are brought into close spatial approximation. The stability of the helical configuration can be attributed to hydrogen bonds between these peptide bonds.

In addition to hydrogen bonds, there are electrostatic interactions, such as those between COO⁻ and NH₃⁺ groups of the side chains, and van der Waals forces, that is, hydrophobic interactions, which help to determine the configuration of the polypeptide chain. The term secondary structure is used to refer to all those structural features of the polypeptide chain determined by noncovalent bonding interactions.

In addition to the α-helical sections of proteins, there are segments that contain β-structures in which there are hydrogen bonds between two polypeptide chains that run in parallel or antiparallel fashion.

The tertiary structure (third level of folding) of a protein comes about through various interactions between different parts of the molecule. Disulfide bridges formed between cysteine residues at different locations in the molecule can stabilize parts of a three-dimensional structure by introducing a primary valence bond as a cross-link. Hydrogen bonds between different segments of the protein, hydrophobic bonds between nonpolar side chains of amino acids such a phenylalanine and leucine, and salt bridges such as those between positively charged lysyl side chains and negatively charged aspartyl side chains all contribute to the individual tertiary structure of a protein.

Finally, for those proteins that contain more than one polypeptide chain per molecule, there is usually a high degree of interaction between each subunit, for example, between the α- and β-polypeptide chains of hemoglobin. This feature of the protein structure is termed its quarternary structure.

Properties

The properties of proteins are determined in part by their amino acid composition. As macromolecules that contain many side chains that can be protonated and unprotonated depending upon the pH of the medium, proteins are excellent buffers. The fact that the pH of blood varies only very slightly in spite of the numerous metabolic processes in which it participates is due to the very large buffering capacity of the blood proteins.

Biosynthesis

The processes by which proteins are synthesized biologically have become one of the central themes of molecular biology. The sequence of amino acid residues in a protein is controlled by the sequence of the DNA as expressed in messenger RNA at ribosomes.

Degradation

As with many other macromolecular components of the organism, most body proteins are in a dynamic state of synthesis and degradation (proteolysis). During proteolysis, the peptide bond that links the amino acids to each other is hydrolyzed, and free amino acids are released. The process is carried out by a diverse group of enzymes called proteases. During proteolysis, the energy invested in generation of the proteins is released. See also Enzyme.

Distinct proteolytic mechanisms serve different physiological requirements. Proteins can be divided into extracellular and intracellular, and the two groups are degraded by two distinct mechanisms. Extracellular proteins such as the plasma immunoglobulins and albumin are degraded in a process known as receptor-mediated endocytosis. Ubiquitin-mediated proteolysis of a variety of cellular proteins plays an important role in many basic cellular processes such as the regulation of cell cycle and division, differentiation, and development; DNA repair; regulation of the immune and inflammatory responses; and biogenesis of organelles.

Molecular chaperones

Molecular chaperones are specialized cellular proteins that bind nonnative forms of other proteins and assist them to reach a functional conformation. The role of chaperone proteins under conditions of stress, such as heat shock, is to protect proteins by binding to misfolded conformations when they are just starting to form, preventing aggregation; then, following return of normal conditions, they allow refolding to occur. Chaperones also play essential roles in folding under normal conditions, providing kinetic assistance to the folding process, and thus improving the overall rate and extent of productive folding.

Protein engineering

The amino acid sequences, sizes, and three-dimensional conformations of protein molecules can be manipulated by protein engineering, in which the basic techniques of genetic engineering are used to alter the genes that encode proteins. These manipulations are used to generate proteins with novel activities or properties for specific applications, to discover structure-function relationships, and to generate biologically active minimalist proteins (containing only those sequences necessary for biological activity) that are smaller than their naturally occurring counterparts.

Many subtle variations in a particular protein can be generated by making amino acid replacements at specific positions in the polypeptide sequence. For example, at any specific position an amino acid can be replaced by another to generate a mutant protein that may have different characteristics by virtue of the single replaced amino acid. Amino acids can also be deleted from a protein sequence, either individually or in groups. These proteins are referred to as deletion mutants. Deletion mutants may or may not be missing one or more functions or properties of the full, naturally occurring protein. Moreover, part or all of a protein sequence can be joined or fused to that of another protein. The resulting protein is called a hybrid or fusion protein, which generally has characteristics that combine those of each of the joined partners.

All living tissues contain proteins; they are polymers of amino acids, joined by peptide bonds. The name was coined by the Dutch chemist Gerard Johann Mulder (1838) meaning ‘of the first importance’. There are twenty main amino acids in proteins, and any one protein may contain several hundred or over a thousand amino acids, so an enormous variety of different proteins occur in nature, i.e. in foods and our bodies.

Generally a polymer of relatively few amino acids is referred to as a peptide (e.g. di-, tri-, and tetrapeptides); oligopeptides contain up to about 50 amino acids; larger molecules are polypeptides or proteins.

The sequence of the amino acids in a protein determines its overall structure and function: many proteins are enzymes; others are structural (e.g. collagen in connective tissue and keratin in hair and nails); many hormones are polypeptides.

Proteins are constituents of all living cells and are dietary essentials. Chemically they are distinguished from fats and carbohydrates by containing nitrogen. They are composed of carbon, hydrogen, oxygen, nitrogen, sulphur, and sometimes phosphorus.

Proteins have been described as the very stuff of life. The word ‘protein’ is from a Greek word meaning ‘of first importance’. This aptly describes the vital part proteins have in the structure and function of every living cell in the body. They comprise between 10-30 per cent of cell mass. They have many varied roles, acting as enzymes, hormones, respiratory pigments (haemoglobin is a protein), and antibodies. The two main contractile elements in muscle cells, actin, and myosin, are proteins.

Chemically, proteins are a group of organic compounds containing carbon, hydrogen, oxygen, and nitrogen. They consist of large molecules, or polymers, containing chains of amino acids linked together by peptide bonds.

Protein consumed in foods is digested in the stomach and small intestine into amino acids which are absorbed into the bloodstream and taken to the liver for initial processing. Some amino acids are transported to muscles and tissues where they are rebuilt into protein. According to the UK Dietary Reference Values, the amount of protein sufficient for most individuals aged 19 or over is 0.75 g per kg per day (about 45 g for the average female and 55.5 g for the average male). Those who are very active, suffering from severe illness, or recovering from surgery need more protein. For example, in a report of an international conference on Foods, Nutrition and Soccer Performance held in Zurich in 1994, sports nutritionists stated that soccer players require between 1.4 to 1.7 grams of protein per kilogram body weight. Protein requirements are also relatively high in children, pregnant women, and nursing mothers. Very active people can meet the body's demands for extra protein by having a well-balanced diet adjusted to their higher energy requirements. Attempts to increase muscle size artificially by consuming excessively high protein diets are thought by most dietitians to be useless. As protein in the diet increases, proportionately less is absorbed from the intestine. Amino acids not needed for growth or repair of body tissues are broken down and excreted as urea, or converted into either glucose (to be used as an energy source) or body fat. One gram of protein yields about 4 Calories. Protein can supply up to 10 per cent of the energy needed to sustain prolonged exercise.

Consumption of excess protein may cause dehydration and constipation, and can lead to obesity. It may also cause deficiencies in vitamin B₆, and a loss of calcium with an increased risk of osteoporosis, but these effects are not fully established. Protein deficiency causes profound weight loss, mental and physical retardation in children, oedema, and anaemia.

Protein-rich foods include meat products, grains, legumes, and vegetables. See also amino acids.

Any one of a group of complex organic nitrogenous compounds; the principal constituent of cell protoplasm. Polymers of amino acids that are joined by peptide or amide bonds.

Proteins are polymers of amino acids that provide structure and control reactions in all cells. When humans think of expressing the meaning of life, they often resort to words. From poems to sonnets to short stories to novels, words tell the stories of life. But in biological terms, the words of life are proteins. While DNA holds the code of life, proteins are the language in which that code is expressed.

To observe the mosaic of proteins in life is to observe nature in its finest array. The feathers of a bird and the silk of a spider's web are both almost pure protein. The most numerous proteins in an animal are the collagen proteins joining animal body parts. Other proteins include the positively charged histone proteins that condense the cell's negatively charged DNA and the transcription factor proteins that control which genes are expressed (made into proteins) and which remain silent. A plant traps CO₂ to make sugar with Earth's most abundant protein, the enzyme ribulose 1,5-biphosphate carboxylase. The protein hemoglobin transports gases through the bloodstream necessary for the metabolism of life. Other proteins store minerals (ferritin) or fats (ovalbumin), contract muscles (myosin), protect against infection (anti-bodies), or act as toxins (botulinum) or hormones (insulin).

Properties of Amino Acids

The English language consists of thousands of words, created from any of twenty-six letters arranged in a precise order. In an analogous fashion, proteins are made up of twenty common amino acids in a precise order dictating the protein's structure and function. Every amino acid has a common structure, in which a central carbon is covalently bonded to a carboxyl group (COOH), an amino group (NH₂), a hydrogen, and a variable "R" group.

The chemical properties of the R group are what give an amino acid its character. The R group can be hydrophilic (attracted to water and other polar molecules) or hydrophobic (attracted to nonpolar molecules and repelled by water or other polar molecules). Hydrophilic R groups can have basic charges, as in the amino acid valine, or acidic, as in glutamic acid, or they may even be an uncharged polar group such as-OH (alcohol) or-NH₂ (amino), as in serine. A nonpolar or hydrophobic R group can be a hydro-carbon chain, as in leucine. There are also three special amino acids: cysteine, glycine, and proline. Cysteine has a reactive sulfhydryl R group that forms disulfide bridges (S-S) between regions of the protein chain. These bridges increase toughness and resistance to unfolding of the protein structure. Glycine is the smallest amino acid, with hydrogen as its R group, and it fits into tight places within a protein's structure. Proline has a cyclic ring involving the central carbon, and it causes kinks to occur in a protein chain. Both proline and glycine are common at the corner of turns in the protein foldings.

Primary Structure

The unique sequence of amino acids in a protein is termed the primary structure. When amino acids form a protein chain, a unique bond, termed the peptide bond, exists between two amino acids. The sequence of a protein begins with the amino of the first amino acid and continues to the carboxyl end of the last amino acid.

The unique sequence of amino acids results from the translation of codons present in messenger RNA (mRNA). The mRNA, in turn, is a complementary copy of the gene that codes for that protein. Protein structure and function can change when "misspellings" occur in the order of amino acids during their transcription and translation. Sickle-cell hemoglobin, for example, is "misspelled" in only one amino acid; the sixth amino acid in the beta chain, where a valine is substituted for a glutamic acid. This occurs because the codon for valine, GUG, has replaced the codon for glutamic acid, GAG. This change from acidic to basic amino acid causes the hemoglobin molecules to stick to one another, forming long chains and blocking oxygen binding. These chains of hemoglobin precipitate in the cell, causing the red blood cells to assume a sickle shape. All of these structural and functional changes occur because of the mutation in the hemoglobin gene and a "misspelling" in the hemoglobin's amino acid sequence.

Secondary Structure and Motifs

The secondary structure of proteins is due to foldings that occur within their structure. These foldings are either in a helical shape, called the "alpha-helix" (which was first proposed by Linus Pauling), or a beta-pleated sheet shaped similar to the zig-zag foldings of an accordion. The turns of the alpha-helix are stabilized by hydrogen bonding between every fourth amino acid in the chain. The alpha-helix can cover specific regions of the protein or it may involve the entire protein, as in the alpha-keratin found in claws and horns. The two sides of the alpha-helix may differ in polarity, with hydrophilic R groups projecting to the lining of the channel, while hydrophobic R groups project to the outside of the channel, where they embed in the hydrophobic membrane. This structure is exemplified in membrane channel proteins, proteins that channel ions across from one surface to another. The beta-pleated sheet is formed by folding successive planes. Each plane is five to eight amino acids long. The folds are stabilized by hydrogen bonding. The strength observed in silk fibers is due to their stacks of beta-pleated sheets.

Combinations of secondary structure form "motifs." A coiled-coil motif is common among proteins that associate with the DNA helix. The helix-loop-helix motif is a knobby structure, and the zinc finger projects outward like its name. These last two motifs allow associations between RNA and proteins that form the basis of their interactions.

Tertiary Structure and Protein Domains

Domains are large functional regions of the protein, such as an enzyme's active site, which binds the substrate to the enzyme. Myoglobin, the muscle protein that stores and releases oxygen, contains several alpha-helices wound around a central crevice. It is in this central crevice that the O₂ molecule binds. Just as words take on their meanings when completed, the functional domains unite to form the overall purpose of a protein. For example, a membrane protein stabilizes itself by anchoring itself with a hydrophilic cytoplasmic domain, then weaves its alpha-helices throughout the membrane domain and projects its carbohydrate hydrophilic side chains into the extracellular surface domain. Such membrane proteins often act as receptors, important for receiving signals such as hormones, or work in the immune system to recognize infected cells.

The local foldings, evident in secondary structure, then combine into a single polypeptide chain. This chain is called the tertiary structure, or conformation. For example, the pancreatic enzyme ribonuclease, which aids in digestion of RNA in the diet, consists mainly of beta sheet folds, with three small alpha-helical regions. Tertiary structure is often stabilized by disulfide bonds between adjacent cysteine in different regions of the protein. For example, the tertiary structure of ribonuclease contains four disulfide bonds, located at specific sites. The stability of the tertiary structure of proteins is destroyed by toxic heavy metals such as mercury. Concentrations of mercury in the environment, for example, result in the displacement of hydrogen on the sulfur atom (SH), thereby blocking functional disulfide bonds.

Several other weak, noncovalent interactions also help stabilize tertiary structure. These noncovalent interactions can be disrupted by heating a protein or exposing it to extremes in pH (acidity or alkalinity), which alters the charge of polar groups on the amino acids. Such disruptions cause the protein to unfold, often exposing hydrophobic groups and leading to precipitation (clumping together) of the protein. If these disruptive factors are removed, some proteins can refold to their original conformation. This ability to refold confirms that protein folding is a self-assembly process that is dependent upon the sequence of amino acids.

Quaternary Structure

Some proteins need to functionally associate with others as subunits in a multimeric structure. This is called the quaternary structure of the protein. This can also be stabilized by disulfide bonds and by noncovalent interactions with reacting substrates or cofactors. For example an antibody consists of two "light" polypeptide chains covalently linked to two longer "heavy" chains, forming a Y-shaped molecule with each branch able to bond to an identical antigen. The protein subunits of the single-stranded binding protein of Escherichia coli bind to DNA only as a tetramer (a multimeric form), acting to stabilize the separated DNA strands during replication.

Another excellent example of quaternary structure is that of hemoglobin. Adult hemoglobin consists of two alpha subunits and two beta subunits, held together by noncovalent interactions. Each of the four subunits contains a heme group that binds an oxygen molecule, O₂. This binding of oxygen is a cooperative process whereby the binding of one oxygen molecule occurs slowly, but once achieved then speeds the binding of the remaining three oxygen molecules. The fourth oxygen molecule binds 300 times faster than the first oxygen molecule. This cooperativity assures that maximum oxygen is captured and retained as it enters into the capillaries within the lungs.

The unloading of oxygen is also facilitated by cooperativity, such that after one oxygen molecule is released, the other three soon follow. This assures that the tissues will receive maximum oxygen once it is delivered. Alpha-hemoglobin by itself, or tetramers of all beta subunits, also bind oxygen, but not with the same cooperativity. Such evidence indicates that there is some form of molecular interaction between the subunits of the tetramer of adult hemoglobin.

Signal Sequences in Protein Synthesis

Protein must be delivered to the proper destination in the cell to function properly. Signal sequences within the protein itself act like "zip codes" to ensure correct delivery. The synthesis of secreted proteins like insulin and of proteins that will be integral to the plasma membrane occurs at a ribo-some tethered to the endoplasmic reticulum, which is a system of membranes that transport materials within cells. The peptides formed there are then translocated into the lumen, or channel, of the endoplasmic reticulum, where they will be formed into a polypeptide chain. This translocation occurs because of a specific signal sequence that is formed by the first twenty or so amino acids in the protein. The core of this sequence consists of ten to fifteen amino acids that have hydrophobic side chains such as alanine, leucine, valine, isoleucine, and phenylalanine, which are usually cleaved from the protein later on. The nascent polypeptide chain is guided along this path by a signal receptor protein.

Proteins targeted for internal cellular functions are synthesized on ribosomal assemblages that float free in the cytoplasm. Such proteins also have their signal sequences. Proteins destined for the cell's nucleus have a specific nuclear signal sequence consisting of a small series of basic amino acids such as arginine and lysine bounded by proline. This nuclear signaling sequence can be located anywhere in the protein's sequence as long as it projects outward from the three-dimensional tertiary structure. Signal sequences for proteins targeted to be part of organelles such as the mitochondria and chloroplasts are anywhere from twenty to seventy amino acids long and are mostly hydrophilic. This charged nature allows easy travel through the hydrophilic cytoplasm to the organelle.

Molecular Chaperones

Although the folding of the protein into its tertiary structure is determined by the primary order of amino acids, the process of folding occurs with the assistance of molecular chaperone proteins. These molecular chaperones often have pockets or tunnels that envelop the nascent polypeptide. This enveloping allows the folding of the protein to occur unhindered by unwanted interaction with other cellular components.

Chemical Modification and Processing of Proteins

Most proteins are structurally altered after synthesis through chemical modification or processing. These alterations help the cell determine a protein's fate, such as whether that protein is active or inactive, how long the protein will function, and to some degree the location where that protein will function. Chemical modifications, which are additions of chemical groups to the R groups in the amino acids, are made after translation. Such modifications may include the attachment of a phosphate group (phosphorylation) to the alcohol group on the amino acids of serine, threonine, or tyrosine. The amino acid proline in proteins such as collagen is often hydroxylated, which means that an alcohol group is attached. Other amino acids with amino groups in their R region, such as lysine or arginine, may be chemically modified through methylation, which is the addition of a methyl group (-CH₃), or through acetylation, in which an acetyl group (-CH₃CO) is added. Larger modifications, such as the addition of a carbohydrate group, occur to create glycoproteins in specialized organelles termed Golgi apparati.

Modifications change the charge of the protein, and often cause a change in the protein's activity level. For many DNA-associated proteins their regional acetylations cause them to "loosen" their grip on the DNA helix, thereby enabling transcription factors to enter, signaling gene activation. A cascade of internal protein phosphorylation (successive additions of a phosphate group) is a common mechanism for carrying a hormone's message from the membrane, where it docks into the cell and induces a metabolic change inside the target cell.

Processing results in cutting off specific parts of the protein (cleavage). Many digestive proteins such as pepsin and hormones such as insulin are processed. Pepsin, which is a digestive protein secreted into the lumen of the stomach, remains in an inactive form until stomach acid is also secreted. The timing of the acid secretion, pepsin activation, and entry of food coincide so that pepsin's activity will be directed toward the food and not the wall of the stomach.

Conformational Changes in Protein Structure

As noted above, a protein's activity can be regulated when it undergoes a change in its conformation. A dramatic and extensively studied model of protein conformational change is that of the Na⁺/K⁺ ATPase pump. This is an integral membrane protein with one side facing the exterior of the cell and the other facing the cytosol. It is used for the specific transport of sodium or potassium across the membrane, and one of its most important functions is the repolarization of a nerve fiber after it "fires."

The first step in the transport process is the binding of three Na⁺ (sodium) ions to the inside face of the protein. This is followed by protein phosphorylation using ATP, which causes the protein to change its conformation. This moves the sodium ions from the cytosol to the exterior. This conformational change also opens up exterior binding sites, which tightly bind two potassium ions outside the cell. Following the potassium binding, the protein is dephosphorylated, losing its recently added phosphate group. This dephosphorylation then changes the protein back to the original conformation, causing the protein to loosen its binding of potassium and deliver those two ions to the cytosol. This process demonstrates that protein structure can be reversibly changed. The net result is that the inside of the cell develops a slight negative charge compared to the outside. The disruption of this "polarized" state constitutes nerve cell firings, which allow the cells of the nervous system to communicate with one another.

Proteomics

Proteomics is a new field of study that seeks to describe which proteins are expressed in a cell, when they are expressed, what consequences result from their expression, and how they fit into biochemical pathways. The first step in the study of proteomics is to define the language of protein structure. The field of proteomics promises to bring a complex understanding to the role of proteins in living cells.

Bibliography

Fairbanks, Daniel, J., and W. Ralph Anderson. Genetics: The Continuity of Life. PacificGrove, CA: Brooks/Cole, 1999.

Lodish, Harvey, et al. Molecular Cell Biology, 4th ed. New York: W. H. Freeman, 2000.

Sadava, David E. Cell Biology: Organelle Structure and Function. Boston: Jones and Bartlett, 1993.

Stryer, Lubert. Biochemistry, 3rd ed. New York: W. H. Freeman, 1988.

—Paul K. Small

A member of a group of organic polymers containing chains of amino acids linked together by peptide bonds. Proteins play a vital part in the structure and function of all cells, comprising 10-30% of cell mass. Structurally, they are divided into two main groups: fibrous proteins and globular proteins. Functionally, they have many varied roles, acting as enzymes, hormones, respiratory pigments, and antibodies. Excess protein cannot be stored in the body and is excreted, mainly as urea in the urine. Each gram of protein contains about 4 kcal of energy. Protein can supply up to 10% of the energy needed to sustain an endurance activity. A diet containing 30-15% of calories from protein should be adequate for most athletes. The World Health Organization recommend a daily protein intake of l g kg body weight⁻¹: studies by sports nutritionists indicate that athletes involved in prolonged heavy training require more protein, about 1.2-1.7 g kg body weight⁻¹. There is little scientific evidence to support the use of very high-protein diets by athletes. On the contrary, these diets could damage the kidneys, and can cause dehydration and constipation. Protein-rich foods include meat, grains, and legumes.

Complex organic molecules made up of amino acids. Proteins are basic components of all living cells and are therefore among the principal substances that make up the body. In addition to being necessary for the growth and repair of the body's tissues, proteins provide energy and act as enzymes that control chemical reactions in the cell.

Pertaining to or of the nature of protein.

This article is part of the series on: Gene expression a Molecular biology topic (portal) (Glossary)

Introduction to Genetics

General flow: DNA > RNA > Protein

special transfers (RNA > RNA, RNA > DNA, Protein > Protein)

Genetic code

Transcription

Transcription (Transcription factors, RNA Polymerase,promoter) Prokaryotic / Archaeal / Eukaryotic

post-transcriptional modification (hnRNA,Splicing)

Translation

Translation (Ribosome,tRNA) Prokaryotic / Archaeal / Eukaryotic

post-translational modification (functional groups, peptides, structural changes)

gene regulation

epigenetic regulation (Genomic imprinting)

transcriptional regulation

post-transcriptional regulation (sequestration, alternative splicing,miRNA)

translational regulation

post-translational regulation (reversible,irreversible)

ask a question , edit

This article is about a class of molecules. For protein as a nutrient, see Protein (nutrient). For other uses, see Protein (disambiguation).

A representation of the 3D structure of myoglobin showing coloured alpha helices. This protein was the first to have its structure solved by X-ray crystallography.

Proteins (also known as polypeptides) are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code.^[1] In general, the genetic code specifies 20 standard amino acids; however, in certain organisms the genetic code can include selenocysteine — and in certain archaea — pyrrolysine. Shortly after or even during synthesis, the residues in a protein are often chemically modified by post-translational modification, which alters the physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Proteins can also work together to achieve a particular function, and they often associate to form stable complexes.^[2]

Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms and participate in virtually every process within cells. Many proteins are enzymes that catalyze biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, which form a system of scaffolding that maintains cell shape. Other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. Proteins are also necessary in animals' diets, since animals cannot synthesize all the amino acids they need and must obtain essential amino acids from food. Through the process of digestion, animals break down ingested protein into free amino acids that are then used in metabolism.

Proteins were first described by the Dutch chemist Gerhardus Johannes Mulder and named by the Swedish chemist Jöns Jakob Berzelius in 1838. The central role of proteins in living organisms was however not fully appreciated until 1926, when James B. Sumner showed that the enzyme urease was a protein.^[3] The first protein to be sequenced was insulin, by Frederick Sanger, who won the Nobel Prize for this achievement in 1958. The first protein structures to be solved were hemoglobin and myoglobin, by Max Perutz and Sir John Cowdery Kendrew, respectively, in 1958.^[4][5] The three-dimensional structures of both proteins were first determined by x-ray diffraction analysis; Perutz and Kendrew shared the 1962 Nobel Prize in Chemistry for these discoveries. Proteins may be purified from other cellular components using a variety of techniques such as ultracentrifugation, precipitation, electrophoresis, and chromatography; the advent of genetic engineering has made possible a number of methods to facilitate purification. Methods commonly used to study protein structure and function include immunohistochemistry, site-directed mutagenesis, and mass spectrometry.

Contents 1 Biochemistry 2 Synthesis 2.1 Chemical synthesis 3 Structure of proteins 3.1 Structure determination 4 Cellular functions 4.1 Enzymes 4.2 Cell signaling and ligand binding 4.3 Structural proteins 5 Methods of study 5.1 Protein purification 5.2 Cellular localization 5.3 Proteomics and bioinformatics 5.4 Structure prediction and simulation 6 Nutrition 7 History and etymology 8 See also 9 Footnotes 10 References 11 External links 11.1 Databases and projects 11.2 Tutorials and educational websites

Biochemistry

Main articles: Biochemistry, Amino acid, and peptide bond

Resonance structures of the peptide bond that links individual amino acids to form a protein polymer.

Proteins are linear polymers built from series of up to 20 different L-α-amino acids. All amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this basic structure as it contains an unusual ring to the N-end amine group, which forces the CO–NH amide moiety into a fixed conformation.^[6] The side chains of the standard amino acids, detailed in the list of standard amino acids, have a great variety of chemical structures and properties; it is the combined effect of all of the amino acid side chains in a protein that ultimately determines its three-dimensional structure and its chemical reactivity.^[7]

Chemical structure of the peptide bond (left) and a peptide bond between leucine and threonine (right).

The amino acids in a polypeptide chain are linked by peptide bonds. Once linked in the protein chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen, and oxygen atoms are known as the main chain or protein backbone.^[8] The peptide bond has two resonance forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar. The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone.^[9] The end of the protein with a free carboxyl group is known as the C-terminus or carboxy terminus, whereas the end with a free amino group is known as the N-terminus or amino terminus.

The words protein, polypeptide, and peptide are a little ambiguous and can overlap in meaning. Protein is generally used to refer to the complete biological molecule in a stable conformation, whereas peptide is generally reserved for a short amino acid oligomers often lacking a stable three-dimensional structure. However, the boundary between the two is not well defined and usually lies near 20–30 residues.^[10] Polypeptide can refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of a defined conformation.

Synthesis

Main article: Protein biosynthesis

The DNA sequence of a gene encodes the amino acid sequence of a protein.

Proteins are assembled from amino acids using information encoded in genes. Each protein has its own unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein. The genetic code is a set of three-nucleotide sets called codons and each three-nucleotide combination designates an amino acid, for example AUG (adenine-uracil-guanine) is the code for methionine. Because DNA contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code, with some amino acids specified by more than one codon.^[11] Genes encoded in DNA are first transcribed into pre-messenger RNA (mRNA) by proteins such as RNA polymerase. Most organisms then process the pre-mRNA (also known as a primary transcript) using various forms of post-transcriptional modification to form the mature mRNA, which is then used as a template for protein synthesis by the ribosome. In prokaryotes the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the nucleoid. In contrast, eukaryotes make mRNA in the cell nucleus and then translocate it across the nuclear membrane into the cytoplasm, where protein synthesis then takes place. The rate of protein synthesis is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second.^[12]

The process of synthesizing a protein from an mRNA template is known as translation. The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme aminoacyl tRNA synthetase "charges" the tRNA molecules with the correct amino acids. The growing polypeptide is often termed the nascent chain. Proteins are always biosynthesized from N-terminus to C-terminus.^[11]

The size of a synthesized protein can be measured by the number of amino acids it contains and by its total molecular mass, which is normally reported in units of daltons (synonymous with atomic mass units), or the derivative unit kilodalton (kDa). Yeast proteins are on average 466 amino acids long and 53 kDa in mass.^[10] The largest known proteins are the titins, a component of the muscle sarcomere, with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids.^[13]

Chemical synthesis

Short proteins can also be synthesized chemically by a family of methods known as peptide synthesis, which rely on organic synthesis techniques such as chemical ligation to produce peptides in high yield.^[14] Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of fluorescent probes to amino acid side chains.^[15] These methods are useful in laboratory biochemistry and cell biology, though generally not for commercial applications. Chemical synthesis is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native tertiary structure. Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction.^[16]

Structure of proteins

Main article: Protein structure

Three possible representations of the three-dimensional structure of the protein triose phosphate isomerase. Left: all-atom representation colored by atom type. Middle: Simplified representation illustrating the backbone conformation, colored by secondary structure. Right: Solvent-accessible surface representation colored by residue type (acidic residues red, basic residues blue, polar residues green, nonpolar residues white).

Most proteins fold into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its native conformation.^[17] Although many proteins can fold unassisted, simply through the chemical properties of their amino acids, others require the aid of molecular chaperones to fold into their native states.^[18] Biochemists often refer to four distinct aspects of a protein's structure:^[19]

• Primary structure: the amino acid sequence.
• Secondary structure: regularly repeating local structures stabilized by hydrogen bonds. The most common examples are the alpha helix, beta sheet and turns. Because secondary structures are local, many regions of different secondary structure can be present in the same protein molecule.
• Tertiary structure: the overall shape of a single protein molecule; the spatial relationship of the secondary structures to one another. Tertiary structure is generally stabilized by nonlocal interactions, most commonly the formation of a hydrophobic core, but also through salt bridges, hydrogen bonds, disulfide bonds, and even post-translational modifications. The term "tertiary structure" is often used as synonymous with the term fold. The Tertiary structure is what controls the basic function of the protein.
• Quaternary structure: the structure formed by several protein molecules (polypeptide chains), usually called protein subunits in this context, which function as a single protein complex.

Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their functions. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as "conformations", and transitions between them are called conformational changes. Such changes are often induced by the binding of a substrate molecule to an enzyme's active site, or the physical region of the protein that participates in chemical catalysis. In solution proteins also undergo variation in structure through thermal vibration and the collision with other molecules.^[20]

Molecular surface of several proteins showing their comparative sizes. From left to right are: immunoglobulin G (IgG, an antibody), hemoglobin, insulin (a hormone), adenylate kinase (an enzyme), and glutamine synthetase (an enzyme).

Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: globular proteins, fibrous proteins, and membrane proteins. Almost all globular proteins are soluble and many are enzymes. Fibrous proteins are often structural, such as collagen, the major component of connective tissue, or keratin, the protein component of hair and nails. Membrane proteins often serve as receptors or provide channels for polar or charged molecules to pass through the cell membrane.^[21]

A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration, are called dehydrons.^[22]

Structure determination

Discovering the tertiary structure of a protein, or the quaternary structure of its complexes, can provide important clues about how the protein performs its function. Common experimental methods of structure determination include X-ray crystallography and NMR spectroscopy, both of which can produce information at atomic resolution. Dual polarisation interferometry is a quantitative analytical method for measuring the overall protein conformation and conformational changes due to interactions or other stimulus. Circular dichroism is another laboratory technique for determining internal beta sheet/ helical composition of proteins. Cryoelectron microscopy is used to produce lower-resolution structural information about very large protein complexes, including assembled viruses;^[23] a variant known as electron crystallography can also produce high-resolution information in some cases , especially for two-dimensional crystals of membrane proteins.^[24] Solved structures are usually deposited in the Protein Data Bank (PDB), a freely available resource from which structural data about thousands of proteins can be obtained in the form of Cartesian coordinates for each atom in the protein.^[25]

Many more gene sequences are known than protein structures. Further, the set of solved structures is biased toward proteins that can be easily subjected to the conditions required in X-ray crystallography, one of the major structure determination methods. In particular, globular proteins are comparatively easy to crystallize in preparation for X-ray crystallography. Membrane proteins, by contrast, are difficult to crystallize and are underrepresented in the PDB.^[26] Structural genomics initiatives have attempted to remedy these deficiencies by systematically solving representative structures of major fold classes. Protein structure prediction methods attempt to provide a means of generating a plausible structure for proteins whose structures have not been experimentally determined.

Cellular functions

Proteins are the chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes.^[10] With the exception of certain types of RNA, most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an Escherichia coli cell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively.^[27] The set of proteins expressed in a particular cell or cell type is known as its proteome.

The enzyme hexokinase is shown as a simple ball-and-stick molecular model. To scale in the top right-hand corner are two of its substrates, ATP and glucose.

The chief characteristic of proteins that also allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or "pocket" on the molecular surface. This binding ability is mediated by the tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific; for example, the ribonuclease inhibitor protein binds to human angiogenin with a sub-femtomolar dissociation constant (<10⁻¹⁵ M) but does not bind at all to its amphibian homolog onconase (>1 M). Extremely minor chemical changes such as the addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding; for example, the aminoacyl tRNA synthetase specific to the amino acid valine discriminates against the very similar side chain of the amino acid isoleucine.^[28]

Proteins can bind to other proteins as well as to small-molecule substrates. When proteins bind specifically to other copies of the same molecule, they can oligomerize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. Protein-protein interactions also regulate enzymatic activity, control progression through the cell cycle, and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function. Proteins can also bind to, or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows the construction of enormously complex signaling networks.^[29] Importantly, as interactions between proteins are reversible, and depend heavily on the availability of different groups of partner proteins to form aggregates that are capable to carry out discrete sets of function, study of the interactions between specific proteins is a key to understand important aspects of cellular function, and ultimately the properties that distinguish particular cell types^[30][31].

Enzymes

Main article: Enzyme

The best-known role of proteins in the cell is as enzymes, which catalyze chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism, as well as manipulating DNA in processes such as DNA replication, DNA repair, and transcription. Some enzymes act on other proteins to add or remove chemical groups in a process known as post-translational modification. About 4,000 reactions are known to be catalyzed by enzymes.^[32] The rate acceleration conferred by enzymatic catalysis is often enormous — as much as 10¹⁷-fold increase in rate over the uncatalyzed reaction in the case of orotate decarboxylase (78 million years without the enzyme, 18 milliseconds with the enzyme).^[33]

The molecules bound and acted upon by enzymes are called substrates. Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with the substrate, and an even smaller fraction — 3 to 4 residues on average — that are directly involved in catalysis.^[34] The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site.

Cell signaling and ligand binding

Ribbon diagram of a mouse antibody against cholera that binds a carbohydrate antigen

Many proteins are involved in the process of cell signaling and signal transduction. Some proteins, such as insulin, are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues. Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Many receptors have a binding site exposed on the cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell.^[35]

Antibodies are protein components of adaptive immune system whose main function is to bind antigens, or foreign substances in the body, and target them for destruction. Antibodies can be secreted into the extracellular environment or anchored in the membranes of specialized B cells known as plasma cells. Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high.^[36]

Many ligand transport proteins bind particular small biomolecules and transport them to other locations in the body of a multicellular organism. These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is haemoglobin, which transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom.^[37] Lectins are sugar-binding proteins which are highly specific for their sugar moieties. Lectins typically play a role in biological recognition phenomena involving cells and proteins.^[38] Receptors and hormones are highly specific binding proteins.

Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse. Membrane proteins contain internal channels that allow such molecules to enter and exit the cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions.^[39]

Structural proteins

Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are fibrous proteins; for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibers that comprise the cytoskeleton, which allows the cell to maintain its shape and size. Collagen and elastin are critical components of connective tissue such as cartilage, and keratin is found in hard or filamentous structures such as hair, nails, feathers, hooves, and some animal shells.^[40]

Other proteins that serve structural functions are motor proteins such as myosin, kinesin, and dynein, which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single celled organisms and the sperm of many multicellular organisms which reproduce sexually. They also generate the forces exerted by contracting muscles.^[41]

Methods of study

Main article: Protein methods

As some of the most commonly studied biological molecules, the activities and structures of proteins are examined both in vitro and in vivo. In vitro studies of purified proteins in controlled environments are useful for learning how a protein carries out its function: for example, enzyme kinetics studies explore the chemical mechanism of an enzyme's catalytic activity and its relative affinity for various possible substrate molecules. By contrast, in vivo experiments on proteins' activities within cells or even within whole organisms can provide complementary information about where a protein functions and how it is regulated.

Protein purification

Main article: Protein purification

In order to perform in vitro analysis, a protein must be purified away from other cellular components. This process usually begins with cell lysis, in which a cell's membrane is disrupted and its internal contents released into a solution known as a crude lysate. The resulting mixture can be purified using ultracentrifugation, which fractionates the various cellular components into fractions containing soluble proteins; membrane lipids and proteins; cellular organelles, and nucleic acids. Precipitation by a method known as salting out can concentrate the proteins from this lysate. Various types of chromatography are then used to isolate the protein or proteins of interest based on properties such as molecular weight, net charge and binding affinity.^[42] The level of purification can be monitored using various types of gel electrophoresis if the desired protein's molecular weight and isoelectric point are known, by spectroscopy if the protein has distinguishable spectroscopic features, or by enzyme assays if the protein has enzymatic activity. Additionally, proteins can be isolated according their charge using electrofocusing.^[43]

For natural proteins, a series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications. To simplify this process, genetic engineering is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity. Here, a "tag" consisting of a specific amino acid sequence, often a series of histidine residues (a "His-tag"), is attached to one terminus of the protein. As a result, when the lysate is passed over a chromatography column containing nickel, the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded. A number of different tags have been developed to help researchers purify specific proteins from complex mixtures.^[44]

Cellular localization

Proteins in different cellular compartments and structures tagged with green fluorescent protein (here, white).

The study of proteins in vivo is often concerned with the synthesis and localization of the protein within the cell. Although many intracellular proteins are synthesized in the cytoplasm and membrane-bound or secreted proteins in the endoplasmic reticulum, the specifics of how proteins are targeted to specific organelles or cellular structures is often unclear. A useful technique for assessing cellular localization uses genetic engineering to express in a cell a fusion protein or chimera consisting of the natural protein of interest linked to a "reporter" such as green fluorescent protein (GFP).^[45] The fused protein's position within the cell can be cleanly and efficiently visualized using microscopy,^[46] as shown in the figure opposite.

Other methods for elucidating the cellular location of proteins requires the use of known compartmental markers for regions such as the ER, the Golgi, lysosomes/vacuoles, mitochondria, chloroplasts, plasma membrane, etc. With the use of fluorescently-tagged versions of these markers or of antibodies to known markers, it becomes much simpler to identify the localization of a protein of interest. For example, indirect immunofluorescence will allow for fluorescence colocalization and demonstration of location. Fluorescent dyes are used to label cellular compartments for a similar purpose.^[47]

Other possibilities exist, as well. For example, immunohistochemistry usually utilizes an antibody to one or more proteins of interest that are conjugated to enzymes yielding either luminescent or chromogenic signals that can be compared between samples, allowing for localization information. Another applicable technique is cofractionation in sucrose (or other material) gradients using isopycnic centrifugation.^[48] While this technique does not prove colocalization of a compartment of known density and the protein of interest, it does increase the likelihood, and is more amenable to large-scale studies.

Finally, the gold-standard method of cellular localization is immunoelectron microscopy. This technique also uses an antibody to the protein of interest, along with classical electron microscopy techniques. The sample is prepared for normal electron microscopic examination, and then treated with an antibody to the protein of interest that is conjugated to an extremely electro-dense material, usually gold. This allows for the localization of both ultrastructural details as well as the protein of interest.^[49]

Through another genetic engineering application known as site-directed mutagenesis, researchers can alter the protein sequence and hence its structure, cellular localization, and susceptibility to regulation. This technique even allows the incorporation on unnatural amino acids into proteins, using modified tRNAs,^[50] and may allow the rational design of new proteins with novel properties.^[51]

Proteomics and bioinformatics

Main articles: Proteomics and Bioinformatics

The total complement of proteins present at a time in a cell or cell type is known as its proteome, and the study of such large-scale data sets defines the field of proteomics, named by analogy to the related field of genomics. Key experimental techniques in proteomics include 2D electrophoresis,^[52] which allows the separation of a large number of proteins, mass spectrometry,^[53] which allows rapid high-throughput identification of proteins and sequencing of peptides (most often after in-gel digestion), protein microarrays,^[54] which allow the detection of the relative levels of a large number of proteins present in a cell, and two-hybrid screening, which allows the systematic exploration of protein-protein interactions.^[55] The total complement of biologically possible such interactions is known as the interactome.^[56] A systematic attempt to determine the structures of proteins representing every possible fold is known as structural genomics.^[57]

The large amount of genomic and proteomic data available for a variety of organisms, including the human genome, allows researchers to efficiently identify homologous proteins in distantly related organisms by sequence alignment. Sequence profiling tools can perform more specific sequence manipulations such as restriction enzyme maps, open reading frame analyses for nucleotide sequences, and secondary structure prediction. From this data phylogenetic trees can be constructed and evolutionary hypotheses developed using special software like ClustalW regarding the ancestry of modern organisms and the genes they express. The field of bioinformatics seeks to assemble, annotate, and analyze genomic and proteomic data, applying computational techniques to biological problems such as gene finding and cladistics.

Structure prediction and simulation

Main articles: protein structure prediction and List of protein structure prediction software

Complementary to the field of structural genomics, protein structure prediction seeks to develop efficient ways to provide plausible models for proteins whose structures have not yet been determined experimentally ^[58]. The most successful type of structure prediction, known as homology modeling, relies on the existence of a "template" structure with sequence similarity to the protein being modeled; structural genomics' goal is to provide sufficient representation in solved structures to model most of those that remain.^[59] Although producing accurate models remains a challenge when only distantly related template structures are available, it has been suggested that sequence alignment is the bottleneck in this process, as quite accurate models can be produced if a "perfect" sequence alignment is known.^[60] Many structure prediction methods have served to inform the emerging field of protein engineering, in which novel protein folds have already been designed.^[61] A more complex computational problem is the prediction of intermolecular interactions, such as in molecular docking and protein-protein interaction prediction.^[62]

The processes of protein folding and binding can be simulated using such technique as molecular mechanics, in particular, molecular dynamics and Monte Carlo, which increasingly take advantage of parallel and distributed computing (Folding@Home project^[63]; molecular modeling on GPU). The folding of small alpha-helical protein domains such as the villin headpiece^[64] and the HIV accessory protein^[65] have been successfully simulated in silico, and hybrid methods that combine standard molecular dynamics with quantum mechanics calculations have allowed exploration of the electronic states of rhodopsins.^[66]

Nutrition

Further information: Protein in nutrition

Most microorganisms and plants can biosynthesize all 20 standard amino acids, while animals (including humans) must obtain some of the amino acids from the diet.^[27] The amino acids that an organism cannot synthesize on its own are referred to as essential amino acids. Key enzymes that synthesize certain amino acids are not present in animals — such as aspartokinase, which catalyzes the first step in the synthesis of lysine, methionine, and threonine from aspartate. If amino acids are present in the environment, microorganisms can conserve energy by taking up the amino acids from their surroundings and downregulating their biosynthetic pathways.

In animals, amino acids are obtained through the consumption of foods containing protein. Ingested proteins are broken down through digestion, which typically involves denaturation of the protein through exposure to acid and hydrolysis by enzymes called proteases. Some ingested amino acids are used for protein biosynthesis, while others are converted to glucose through gluconeogenesis, or fed into the citric acid cycle. This use of protein as a fuel is particularly important under starvation conditions as it allows the body's own proteins to be used to support life, particularly those found in muscle.^[67] Amino acids are also an important dietary source of nitrogen.^{[citation needed]}

History and etymology

Further information: History of molecular biology

Proteins were recognized as a distinct class of biological molecules in the eighteenth century by Antoine Fourcroy and others, distinguished by the molecules' ability to coagulate or flocculate under treatments with heat or acid. Noted examples at the time included albumin from egg whites, blood serum albumin, fibrin, and wheat gluten. Dutch chemist Gerhardus Johannes Mulder carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula, C₄₀₀H₆₂₀N₁₀₀O₁₂₀P₁S₁.^[68] He came to the erroneous conclusion that they might be composed of a single type of (very large) molecule. The term "protein" to describe these molecules was proposed in 1838 by Mulder's associate Jöns Jakob Berzelius; protein is derived from the Greek word πρωτεῖος (proteios), meaning "primary"^[69], "in the lead", or "standing in front".^[70] Mulder went on to identify the products of protein degradation such as the amino acid leucine for which he found a (nearly correct) molecular weight of 131 Da.^[68]

The difficulty in purifying proteins in large quantities made them very difficult for early protein biochemists to study. Hence, early studies focused on proteins that could be purified in large quantities, e.g., those of blood, egg white, various toxins, and digestive/metabolic enzymes obtained from slaughterhouses. In the 1950s, the Armour Hot Dog Co. purified 1 kg of pure bovine pancreatic ribonuclease A and made it freely available to scientists; this gesture helped ribonuclease A become a major target for biochemical study for the following decades.^[68]

Linus Pauling is credited with the successful prediction of regular protein secondary structures based on hydrogen bonding, an idea first put forth by William Astbury in 1933.^[71] Later work by Walter Kauzmann on denaturation,^[72][73] based partly on previous studies by Kaj Linderstrøm-Lang,^[74] contributed an understanding of protein folding and structure mediated by hydrophobic interactions. In 1949 Fred Sanger correctly determined the amino acid sequence of insulin, thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, colloids, or cyclols.^[75] The first atomic-resolution structures of proteins were solved by X-ray crystallography in the 1960s and by NMR in the 1980s. As of 2009, the Protein Data Bank has over 55,000 atomic-resolution structures of proteins.^[76] In more recent times, cryo-electron microscopy of large macromolecular assemblies^[77] and computational protein structure prediction of small protein domains^[78] are two methods approaching atomic resolution.

See also

• Expression cloning
• Intein
• List of proteins
• List of recombinant proteins
• Prion
• Protein design
• Protein dynamics
• Protein structure prediction software
• Proteopathy
• Proteopedia
• Cdx protein family

Footnotes

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References

• Branden C, Tooze J. (1999). Introduction to Protein Structure. New York: Garland Pub. ISBN 0-8153-2305-0. 
• Murray RF, Harper HW, Granner DK, Mayes PA, Rodwell VW. (2006). Harper's Illustrated Biochemistry. New York: Lange Medical Books/McGraw-Hill. ISBN 0-07-146197-3. 
• Van Holde KE, Mathews CK. (1996). Biochemistry. Menlo Park, Calif: Benjamin/Cummings Pub. Co., Inc. ISBN 0-8053-3931-0. 

External links

• Protein Songs (Stuart Mitchell - DNA Music Project), 'When a "tape" of mRNA passes through the "playing head" of a ribosome, the "notes" produced are amino acids and the pieces of music they make up are proteins.'

Databases and projects

• Comparative Toxicogenomics Database curates protein-chemical interactions, as well as gene/protein-disease relationships and chemical-disease relationships.
• Bioinformatic Harvester A Meta search engine (29 databases) for gene and protein information.
• The Protein Databank (see also PDB Molecule of the Month, presenting short accounts on selected proteins from the PDB)
• Proteopedia - Life in 3D: rotatable, zoomable 3D model with wiki annotations for every known protein molecular structure.
• UniProt the Universal Protein Resource
• Human Protein Atlas
• NCBI Entrez Protein database
• NCBI Protein Structure database
• Human Protein Reference Database
• Human Proteinpedia
• Folding@Home (Stanford University)

Tutorials and educational websites

• "An Introduction to Proteins" from HOPES (Huntington's Disease Outreach Project for Education at Stanford)
• Proteins: Biogenesis to Degradation - The Virtual Library of Biochemistry and Cell Biology

v • d • e Proteins Processes Protein biosynthesis - Posttranslational modification - Protein folding - Protein targeting - Proteome - Protein methods Structures Protein structure - Protein structural domains - Proteasome Types List of types of proteins - List of proteins - Membrane protein - Globular protein (Globulin, Albumin) - Fibrous protein

v • d • e Proteins: key methods of study Experimental Protein purification - Green fluorescent protein - Western blot - Protein immunostaining - Protein sequencing - Gel electrophoresis/Protein electrophoresis - Protein immunoprecipitation - Peptide mass fingerprinting Bioinformatics Protein structure prediction - Protein-protein docking - Protein structural alignment - Protein ontology - Protein-protein interaction prediction Assay Enzyme assay - Protein assay - Secretion assay

v • d • e Proteins: enzymes Topics Active site - Allosteric regulation - Binding site - Catalytically perfect enzyme - Coenzyme - Cofactor - Cooperativity - EC number Enzyme catalysis - Enzyme inhibitor - Enzyme kinetics - Lineweaver–Burk plot - Michaelis–Menten kinetics - List of enzymes Types EC1 Oxidoreductases/list - EC2 Transferases/list - EC3 Hydrolases/list - EC4 Lyases/list - EC5 Isomerases/list - EC6 Ligases/list

v • d • e Proteins of the cytoskeleton Human Microfilaments (ABPs) Myofilament Actins (A1, A2, B, G1, G2) Myosins (1A, 1B, 1C, MYH1, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYH10, MYH11, MYH13, MYH14, MYH15, MYH16) Tropomodulin (1, 2, 3, 4) · Troponin (T 1 2 3, C 1 2, I 1 2 3) · Tropomyosin (1, 2, 3, 4) other related: Actinin (1, 2, 3, 4) · Arp2/3 complex · actin depolymerizing factors (Cofilin (1, 2) · Destrin) · Gelsolin · Profilin (1, 2) Other Wiskott-Aldrich syndrome protein IFs type 1 and 2 (Cytokeratin, type I, type II) · type 3 (Desmin, GFAP, Peripherin, Vimentin) · type 4 (Internexin, Nestin, Neurofilament, Synemin, Syncoilin) · type 5 (Lamin A, B) Microtubules Dyneins · Kinesins · MAPs (Tau protein, Dynamin) · Tubulins · Stathmin · Tektin Catenins Alpha catenin · Beta catenin · Plakoglobin (gamma catenin) · Delta catenin Other APC · Dystrophin (Dystroglycan) · plakin (Desmoplakin, Plectin) · Spectrin (SPTA1, SPTAN1, SPTB, SPTBN1, SPTBN2, SPTBN4, SPTBN5) · Talin (TLN1)  · Utrophin · Vinculin Nonhuman Major sperm proteins · Prokaryotic cytoskeleton (Crescentin, FtsZ, MreB)

v • d • e Proteins: coagulation Coagulation factors Primary hemostasis vWF platelet membrane glycoproteins: Ib (A, B, IX) · IIb/IIIa (IIb, IIIa) · VI Intrinsic pathway HMWK/Bradykinin · Prekallikrein/Kallikrein · XII "Hageman" XI · IX · VIII Extrinsic pathway III "Tissue factor" · VII Common pathway X · V · II "(Pro)thrombin" · I "Fibrin" XIII Coagulation inhibitors Antithrombin (inhibits II, IX, X, XI, XII) · Protein C (inhibits V, VIII)/Protein S (cofactor for protein C) · Protein Z (inhibits X) · ZPI (inhibits X, XI) · TFPI (inhibits III) Thrombolysis/fibrinolysis Plasmin · tPA/urokinase · PAI-1/2 · α2-AP · α2-macroglobulin · TAFI

v • d • e Proteins: complement system (C, L, A) Activators/enzymes Early C: C1Q/C1R/C1S - C4 (C4a) - C2 L: MASP1/MASP2 - MBL Middle CLA: C3 (C3a, C3b/iC3b) - C5 (C5a) A: Factor B - Factor D - Factor P/Properdin CLA: C3-convertase - C5-convertase Late CLA: MAC (C6, C7, C8, C9) Inhibitors CLA: C1-inhibitor - Decay accelerating factor - Factor I CL: C4BP A: Factor H Complement receptors CR1 - CR2 - CR3 - CR4 - CD11b/CD11c/CD18 - Anaphylatoxin (C3a, C5a)

v • d • e Proteins: carrier proteins Fatty acid FABP1 · FABP2 · FABP3 · FABP4 · FABP5 · FABP6 · FABP7 Hormone Follistatin · Growth hormone binding protein · Insulin-like growth factor binding protein (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6, IGFBP7) · Neurophysins (Neurophysin I, II) Sex hormone binding globulin/Androgen binding protein · Transcortin · Thyroxine-binding globulin · Transthyretin Metal/element calcium (Calcium-binding protein, Calmodulin-binding proteins) · copper (Ceruloplasmin) · iron (Iron-binding proteins, Transferrin receptor) Vitamin Retinol binding protein (4) · Transcobalamin Other Acyl carrier protein · Adaptor protein · Cholesterylester transfer protein · F-box protein · GTP-binding protein · Latent TGF-beta binding protein · Light-harvesting complex · Membrane transport protein

v • d • e Food chemistry Additives · Carbohydrates · Coloring · Enzymes · Essential fatty acids · Flavors · Lipids · Minerals · Proteins · Vitamins · Water

v • d • e Metabolism (Catabolism, Anabolism) General Metabolic pathway · Metabolic network · Cellular respiration (Anaerobic/Aerobic) Specific paths Protein metabolism Protein synthesis · Amino acid synthesis · Catabolism Nucleotide metabolism: Purine metabolism  · Nucleotide salvage · Pyrimidine metabolism Carbohydrate metabolism Anabolism Gluconeogenesis · Glycogenesis · Photosynthesis (Carbon fixation) Carbohydrate catabolism Glycolysis · Glycogenolysis · Fermentation (Ethanol, Lactic acid)  · Cellular respiration · Xylose metabolism Other Pentose phosphate pathway Lipid metabolism Fatty acid metabolism Fatty acid degradation (Lipolysis, Beta oxidation) · Fatty acid synthesis Other Eicosanoid metabolism · Sphingolipid metabolism · Steroid metabolism Other Metal metabolism (Iron metabolism) · Ethanol metabolism

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)

Common misspelling(s) of protein

• protem

Dansk (Danish)
n. - protein, æggehvidestof

Nederlands (Dutch)
proteïne, eiwit

Français (French)
n. - protéine

Deutsch (German)
n. - Protein, Eiweiß

Ελληνική (Greek)
n. - (βιολ.) πρωτεϊνη

Italiano (Italian)
proteina

Português (Portuguese)
n. - proteína (f)

Русский (Russian)
протеин

Español (Spanish)
n. - proteína

Svenska (Swedish)
n. - protein

中文（简体）(Chinese (Simplified))
蛋白质

中文（繁體）(Chinese (Traditional))
n. - 蛋白質

한국어 (Korean)
n. - 단백질

日本語 (Japanese)
n. - タンパク質

العربيه (Arabic)
‏(الاسم) مادة آحيه, بروتين‏

עברית (Hebrew)
n. - ‮חלבון‬

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