lectin

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Lectins are sugar-binding proteins which are highly specific for their sugar moieties. They typically play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection.

lateral hemagglutinine

Leucoagglutinin, a toxic phytohemagglutinin found in raw Vicia faba

Etymology

The name "lectin" is derived from the Latin word legere, meaning, among other things, "to select".

History

Although they were first discovered more than 100 years ago in plants, they are now known to be present throughout nature. It is generally believed that the earliest description of such a hemagglutinin was by Peter Hermann Stillmark in his doctoral thesis presented in 1888 to the University of Dorpat, (one of the oldest universities in czarist Russia). This hemagglutinin, which was also highly toxic, was isolated by Stillmark from seeds of the castor tree (Ricinus communis) and was named ricin. The first lectin to be purified on a large scale and available on a commercial basis was concanavalin A, which is now the most used lectin for characterization and purification of sugar-containing molecules and cellular structures.

Biological functions

Most lectins are basically non-enzymic in action and non-immune in origin. Lectins occur ubiquitously in nature. They may bind to a soluble carbohydrate or to a carbohydrate moiety which is a part of a glycoprotein or glycolipid. They typically agglutinate certain animal cells and/or precipitate glycoconjugates.

An oligosaccharide (shown in grey) bound in the binding site of a plant lectin (Griffonia simplicifolia isolectin IV in complex with the Lewis b blood group determinant). Only a part of the oligosaccharide (central, in grey) is shown for clarity.

Function in animals

Lectins serve many different biological functions in animals, from the regulation of cell adhesion to glycoprotein synthesis and the control of protein levels in the blood. They may also bind soluble extracellular and intercellular glycoproteins.

Some lectins are found on the surface of mammalian liver cells which specifically recognize galactose residues. It is believed that these cell-surface receptors are responsible for the removal of certain glycoproteins from the circulatory system.

Another lectin is a receptor which recognizes hydrolytic enzymes containing mannose-6-phosphate, and subsequently targets these proteins for delivery to the lysosomes. I-cell disease is one type of defect in this particular system.

Lectins are also known to play important roles in the immune system by recognizing carbohydrates that are found exclusively on pathogens, or that are inaccessible on host cells. Examples are the lectin complement activation pathway and mannose binding lectin.

Function in plants

The function of lectins in plants is still uncertain. Once thought to be necessary for rhizobia binding, this proposed function was ruled out through lectin-knockout transgene studies.^{[citation needed]}

The large concentration of lectins in plant seeds decreases with growth, and suggests a role in plant germination and perhaps in the seed's survival itself. The binding of glycoproteins on the surface of parasitic cells is also believed to be a function. Several plant lectins have been found to recognise non-carbohydrate ligands that are primarily hydrophobic in nature, including adenine, auxins, cytokinin and indole acetic acid as well as water-soluble porphyrins. It has been suggested that these interactions may be physiologically relevant since some of these molecules function as phytohormones.^[1]

Use in science, medicine and technology

Use in medicine and medical research

Purified lectins are important in a clinical setting because they are used for blood typing^{[citation needed]}. Some of the glycolipids and glycoproteins on an individual's red blood cells can be identified by lectins.

• A lectin from Dolichos biflorus is used to identify cells that belong to the A1 blood group.
• A lectin from Ulex europaeus is used to identify the H blood group antigen.
• A lectin from Vicia graminea is used to identify the N blood group antigen.

In neuroscience, the anterograde labeling method is used to trace the path of efferent axons with PHA-L, a lectin from the kidney bean.^[2]

Use in studying carbohydrate recognition by proteins

Lectins from legume plants, such as PHA or concanavalin A, have been widely used as model systems to understand the molecular basis of how proteins recognize carbohydrates, because they are relatively easy to obtain and have a wide variety of sugar specificities. The many crystal structures of legume lectins have led to a detailed insight of the atomic interactions between carbohydrates and proteins.

Use as a biochemical tool

Concanavalin A and other commercially available lectins have been widely used in affinity chromatography for purifying proteins. Generally proteins may be characterized with respect to glycoforms and carbohydrate structure by means of affinity chromatography, blotting, affinity electrophoresis and affinity immunoelectrophoreis with lectins.

Use in biochemical warfare

One example of the powerful biological attributes of lectins is the biochemical warfare agent ricin. Ricin is isolated from seeds of the castor oil plant and is a protein that comprises two domains,

• One is a lectin that binds cell surface galactosyl residues and enables the protein to enter cells.
• The second domain is an N-glycosidase that cleaves nucleobases from ribosomal RNA resulting in inhibition of protein synthesis and cell death.

Toxicity

Foods with high concentrations of lectins, such as beans, cereal grains, seeds, and nuts, may be harmful if consumed in excess. Adverse effects include allergic reactions, nutritional deficiencies, and immune reactions. Different foods may have different effects depending on blood type.^[3]

Lectin and Leptin Resistance

According to Jönsson et al, lectin may cause leptin resistance: "Thus, dietary lectins could possibly bind to the leptin receptor and affect its function, which could translate into diseases of affluence as indicated by studies on effects of single nucleotide polymorphisms on the function of leptin and the leptin receptor.

"Leptin administered peripherally in animal models such as rodents promotes weight loss and satiation, but peripheral administration of leptin in obese human does not promote significant weight loss. This difference in effect together with the observation that most obese humans have high levels of leptin suggest that leptin resistance causes human obesity."

"Leptin acts as a signal to the brain to inhibit food intake and enable the storage in adipocytes of surplus calories while simultaneously protecting peripheral non-adipose tissue from toxic effects of intracellular lipid overload [39]. Leptin also affects the growth of blood vessels and bone; the immune system; glucose- and fat metabolism and the reproductive system.^[4]

See also