myosin

Part of the myosin II structure. Atoms in the heavy chain are colored red on the left-hand side, and atoms in the light chains are colored orange and yellow.

Myosins are a large family of motor proteins found in eukaryotic tissues. They are responsible for actin-based motility.

"The term “myosin” was originally used to describe a group of similar, but nonidentical, ATPases found in striated and smooth muscle cells." From Pollard and Korn, 1973^[1]

Following the discovery by Pollard and Korn of enzymes with myosin-like function in Acanthamoeba castellanii, a large number of divergent myosin genes have been discovered throughout eukaryotes. Thus, although myosin was originally thought to be restricted to muscle cells (hence, "myo"), there is no single "myosin" but rather a huge superfamily of genes whose protein products share the basic properties of actin binding, ATP hydrolysis (ATPase enzyme activity), and force transduction. Virtually all eukaryotic cells contain myosin isoforms. Some isoforms have specialized functions in certain cell types (such as muscle), while other isoforms are ubiquitous.

Structure and function

Domains

Most myosin molecules are composed of a head, neck, and tail domain.

• The head domain binds the filamentous actin, and uses ATP hydrolysis to generate force and to "walk" along the filament towards the barbed (+) end (with the exception of myosin VI, which moves towards the pointed (-) end).

• the neck domain acts as a linker and as a lever arm for transducing force generated by the catalytic motor domain. The neck domain can also serve as a binding site for myosin light chains which are distinct proteins that form part of a macromolecular complex and generally have regulatory functions.

• The tail domain generally mediates interaction with cargo molecules and/or other myosin subunits. In some cases, the tail domain may play a role in regulating motor activity.

Power stroke

Multiple myosin II molecules generate force in skeletal muscle through a power stroke mechanism fuelled by the energy released from ATP hydrolysis.^[2] The power stroke occurs at the release of the products of ATP hydrolysis - ADP and phosphate - when myosin is tightly bound to actin. The effect of this release is a conformational change in the molecule that pulls against the actin. The combined effect of the myriad power strokes causes the muscle to contract. See muscle contraction.

Nomenclature, evolution, and the family tree

The wide variety of myosin genes found throughout the eukaryotic phyla were named according to different schemes as they were discovered. The nomenclature can therefore be somewhat confusing when attempting to compare the functions of myosin proteins within and between organisms.

Skeletal muscle myosin, the most conspicuous of the myosin superfamily due to its abundance in muscle fibers, was the first to be discovered. This protein makes up part of the sarcomere and forms macromolecular filaments composed of multiple myosin subunits. Similar filament-forming myosin proteins were found in cardiac muscle, smooth muscle, and non-muscle cells. However, beginning in the 1970s researchers began to discover new myosin genes in simple eukaryotes ^[1] encoding proteins that acted as monomers and were therefore entitled Class I myosins. These new myosins were collectively termed "unconventional myosins" ^[3] and have been found in many tissues other than muscle. These new superfamily members have been grouped according to phylogenetic relationships derived from a comparison of the amino acid sequences of their head domains, with each class being assigned a Roman numeral ^[4][5][6][7](see phylogenetic tree). The unconventional myosins also have divergent tail domains, suggesting unique functions^[8]. The now diverse array of myosins likely evolved from an ancestral precursor (see picture).

Myosin unrooted phylogenetic tree — click on image to see larger version (Source: http://www.mrc-lmb.cam.ac.uk/myosin/trees/trees.html)

Analysis of the amino acid sequences of different myosins shows great variability among the tail domains but strong conservation of head domain sequences. Presumably this is so the myosins may interact, via their tails, with a large number of different cargoes, while the goal in each case - to move along actin filaments - remains the same and therefore requires the same machinery in the motor. For example, the human genome contains over 40 different myosin genes.

These differences in shape also determine the speed at which myosins can move along actin filaments. The hydrolysis of ATP and the subsequent release of the phosphate group causes the "power stroke," in which the "lever arm" or "neck" region of the heavy chain is dragged forward. Since the power stroke always moves the lever arm by the same angle, the length of the lever arm determines how fast the cargo will move. A longer lever arm will cause the cargo to traverse a greater distance even though the lever arm undergoes the same angular displacement - just as a person with longer legs can move farther with each individual step. Myosin V, for example, has a much longer neck region than myosin II, and therefore moves 30-40 nanometers with each stroke as opposed to only 5-10.

Myosin classes

Myosin I

Myosin I functions as monomer and functions in vesicle transport.^[9]

Myosin II

Sliding filament model of muscle contraction.

Myosin II (also known as conventional myosin) is the best-studied example of these properties.

• Myosin II contains two heavy chains, each about 2000 amino acids in length, which constitute the head and tail domains. Each of these heavy chains contains the N-terminal head domain, while the C-terminal tails take on a coiled-coil morphology, holding the two heavy chains together (imagine two snakes wrapped around each other, such as in a caduceus). Thus, myosin II has two heads.

• It also contains 4 light chains (2 per head), which bind the heavy chains in the "neck" region between the head and tail. These light chains are often referred to as the essential light chain and the regulatory light chain.

In muscle cells, it is myosin II that is responsible for producing the contractile force. Here, the long coiled-coil tails of the individual myosin molecules join together, forming the thick filaments of the sarcomere. The force-producing head domains stick out from the side of the thick filament, ready to walk along the adjacent actin-based thin filaments in response to the proper chemical signals.

Myosin III

Myosin IV

Myosin V

Myosin V is an unconventional myosin motor, which is functional as a dimer. It translocates (walks) along actin filaments traveling towards the barbed end (+ end) of the filaments. Myosin V was thought to be critical in vesicle movement from the center of the cell to the periphery, but has been shown to be more like a dynamic tether retaining vesicles and organelles in the actin-rich periphery of cells.

Myosin VI

Myosin VI is an unconventional myosin motor, which is functional as a dimer. It translocates (walks) along actin filaments traveling towards the pointed end of the filaments. It is the only myosin motor class known to translocate towards the pointed end. Myosin VI is thought to transport endocytic vesicles into the cell.

Myosin VII

Myosin VII is an unconventional myosin with two FERM domains in the tail region. It has a very short coiled-coiled region. Myosin VII is required for phagocytosis in Dictyostelium, spermatogenesis in C. elegans and stereocilia formation in mice and zebrafish^[10].

Myosin VIII

Myosin IX

Myosin X

Myosin X is an unconventional myosin motor, which is functional as a dimer. In mammalian cells the motor is found to localize to filopodia. Myosin X walks towards the barbed ends of filaments. Some research suggests that is preferentially walks on bundles of actin, rather than single filaments. It is the first myosin motor to exhibit this behavior.

Myosin XI

Myosin XII

Myosin XIII

Myosin XIV

Myosin XV

Myosin XV is a motor that is involved in the structuring and motion of stereocilia of in the inner ear. It is thought to be functional as a monomer.

Myosin XVI

Myosin XVII

Genes in humans

Note that not all of these genes are active.

• Class I: MYO1A, MYO1B, MYO1C, MYO1D, MYO1E, MYO1F, MYO1G, MYO1H
• Class II: MYH1, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYH10, MYH11, MYH13, MYH14, MYH15, MYH16
• Class III: MYO3A, MYO3B
• Class V: MYO5A, MYO5B, MYO5C
• Class VI: MYO6
• Class VII: MYO7A, MYO7B
• Class IX: MYO9A, MYO9B
• Class X: MYO10
• Class XV: MYO15A
• Class XVIII: MYO18A, MYO18B

Myosin light chains are distinct and have their own properties. They are not considered "myosins" but are components of the macromolecular complexes that make up the functional myosin enzymes.

• Light chain: MYL1, MYL2, MYL3, MYL4, MYL5, MYL6, MYL6B, MYL7, MYL9, MYLIP, MYLK, MYLK2, MYLL1

Paramyosin

Paramyosin is a large 93-115kDa muscle protein that has been described in a number of diverse invertebrate phyla^[11]. It is thought that invertebrate thick filaments are composted of an inner paramyosin core that is surrounded by myosin. The myosin interacts with actin resulting in fibre contraction^[12]. Paramyosin is found in many different invertebrate species, for example, Brachiopoda, Sipunculidea, Nematoda, Annelida, Mollusca, Arachnida, Insecta^[11]. Paramyosin is responsible for the "catch" mechanism that enables sustained contraction of muscles with very little energy expenditure, such that a clam can remain closed for extended periods.

Footnotes

1. ^ ^{a b} Pollard and Korn, 1973
2. ^ Tyska MJ, Warshaw DM (2002). "The myosin power stroke". Cell Motil Cytoskeleton 51 (1): 1–15. doi:10.1002/cm.10014. PMID 11810692. 
3. ^ Cheney and Mooseker, 1992
4. ^ Cheney et al., 1993
5. ^ Goodson, 2004
6. ^ Hodge and Cope, 2000
7. ^ Berg et al., 2001
8. ^ Oliver et al., 1999
9. ^ Sutherland Macive (6/4/03). "Myosin I". http://www.bms.ed.ac.uk/research/others/smaciver/Myosin%20I.htm. Retrieved 2007-05-23. 
10. ^ Schliwa, 2003, pp 516, 518
11. ^ ^{a b} Winkelman, L. 1976
12. ^ Twarog, B. M. 1976

References

• Berg JS, Powell BC, Cheney RE (April 2001). "A millennial myosin census". Mol. Biol. Cell 12 (4): 780–94. PMID 11294886. PMC 32266. http://www.molbiolcell.org/cgi/pmidlookup?view=long&pmid=11294886. 
• Cheney RE, Mooseker MS (February 1992). "Unconventional myosins". Curr. Opin. Cell Biol. 4 (1): 27–35. doi:10.1016/0955-0674(92)90055-H. PMID 1558751. 
• Cheney RE, Riley MA, Mooseker MS (1993). "Phylogenetic analysis of the myosin superfamily". Cell Motil. Cytoskeleton 24 (4): 215–23. doi:10.1002/cm.970240402. PMID 8477454. 
• Hodge T, Cope MJ (October 2000). "A myosin family tree". J. Cell. Sci. 113 Pt 19: 3353–4. PMID 10984423. http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=10984423. 
• Gavin RH (2001). "Myosins in protists". Int. Rev. Cytol. 206: 97–134. doi:10.1016/S0074-7696(01)06020-X. PMID 11407764. 
• Goodson HV (1994). "Molecular evolution of the myosin superfamily: application of phylogenetic techniques to cell biological questions". Soc. Gen. Physiol. Ser. 49: 141–57. PMID 7939893. 
• Mooseker MS, Cheney RE (1995). "Unconventional myosins". Annu. Rev. Cell Dev. Biol. 11: 633–75. doi:10.1146/annurev.cb.11.110195.003221. PMID 8689571. 
• Oliver TN, Berg JS, Cheney RE (October 1999). "Tails of unconventional myosins". Cell. Mol. Life Sci. 56 (3-4): 243–57. doi:10.1007/s000180050426. PMID 11212352. http://link.springer.de/link/service/journals/00018/bibs/90563-4/90560243.htm. 
• Pollard TD, Korn ED (July 1973). "Acanthamoeba myosin. I. Isolation from Acanthamoeba castellanii of an enzyme similar to muscle myosin". J. Biol. Chem. 248 (13): 4682–90. PMID 4268863. http://www.jbc.org/cgi/pmidlookup?view=long&pmid=4268863. 
• Sellers JR (March 2000). "Myosins: a diverse superfamily". Biochim. Biophys. Acta 1496 (1): 3–22. doi:10.1016/S0167-4889(00)00005-7. PMID 10722873. http://linkinghub.elsevier.com/retrieve/pii/S0167-4889(00)00005-7. 
• Soldati T, Geissler H, Schwarz EC (1999). "How many is enough? Exploring the myosin repertoire in the model eukaryote Dictyostelium discoideum". Cell Biochem. Biophys. 30 (3): 389–411. doi:10.1007/BF02738121. PMID 10403058. 
• Twarog, B. M. (1976). Aspects of smooth muscle function in molluscan catch muscle. Current Topics in Physiology 56, 829-838.
• Winkelman, L. (1976). Comparative studies of paramyosins. Comparative Biochemistry and Physiology, Part B, Biochemistry and Molecular Biology 55, 391-397.
• Molecular Biology of the Cell. Alberts, Johnson, Lewis, Raff, Roberts, and Walter. 4th Edition. 949-952.
• Manfred Schliwa, ed (2003). Molecular Motors. Wiley-VCH. ISBN 3-527-30594-7. 

Additional images

Phase 1	Phase 2	Phase 3	Phase 4
Myosin-painting	Myosin powerstroke

See also

• Motor protein
• Actin

External links

• Myosin Video A video of a moving myosin motor protein.
• MeSH Myosins
• The Myosin Homepage
• Animation of a moving myosin motor protein
• EC 3.6.4.1