Myosin

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Part of the myosin II structure. Atoms in the heavy chain are colored pink (on the left-hand side); atoms in the light chains are colored faded-orange and faded-yellow (also on the left-hand side).

Myosins (/ˈmaɪəsɪn, -oʊ-/[1][2]) are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility.

The first myosin (M2) to be discovered was in 1864 by

smooth muscle tissue
.

Following the discovery in 1973 of enzymes with myosin-like function in Acanthamoeba castellanii, a global range of divergent myosin genes have been discovered throughout the realm of eukaryotes.[5]

Although myosin was originally thought to be restricted to muscle cells (hence myo-(s) + -in), there is no single "myosin"; rather it is a very large 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. The structure and function of myosin is globally conserved across species, to the extent that rabbit muscle myosin II will bind to actin from an amoeba.[6]

Structure and functions

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

Main article: Muscle contraction

Multiple myosin II molecules generate force in skeletal muscle through a power stroke mechanism fuelled by the energy released from ATP hydrolysis.[7] The power stroke occurs at the release of phosphate from the myosin molecule after the ATP hydrolysis while myosin is tightly bound to actin. The effect of this release is a conformational change in the molecule that pulls against the actin. The release of the ADP molecule leads to the so-called rigor state of myosin.[8] The binding of a new ATP molecule will release myosin from actin. ATP hydrolysis within the myosin will cause it to bind to actin again to repeat the cycle. The combined effect of the myriad power strokes causes the muscle to contract.

Nomenclature, evolution, and the family tree

Myosin unrooted phylogenetic 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

Roman numeral[10][11][12][13] (see phylogenetic tree). The unconventional myosins also have divergent tail domains, suggesting unique functions.[14] The now diverse array of myosins likely evolved from an ancestral precursor
(see picture).

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

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 the displacement of the cargo relative to the actin filament. 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. The velocity of a myosin motor depends upon the rate at which it passes through a complete kinetic cycle of ATP binding to the release of ADP.

Myosin classes

Myosin I

Myosin I, a ubiquitous cellular protein, functions as monomer and functions in

vesicle transport.[15] It has a step size of 10 nm and has been implicated as being responsible for the adaptation response of the stereocilia in the inner ear.[16]

Myosin II

Sliding filament model
of muscle contraction.
Cardiac sarcomere structure featuring myosin

Myosin II (also known as conventional myosin) is the myosin type responsible for producing muscle contraction in muscle cells in most animal cell types. It is also found in non-muscle cells in contractile bundles called stress fibers.[17]

In muscle cells, the long

coiled-coil tails of the individual myosin molecules join, 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.

Further information: Muscle contraction
Further information: Meromyosin

Myosin III

Myosin III is a poorly understood member of the myosin family. It has been studied

MYO3A, has been uncovered through the Human Genome Project and is expressed in the retina and cochlea.[21]

Crystal structure of myosin V motor with essential light chain – nucleotide-free

Myosin IV

Myosin IV has a single

IQ motif and a tail that lacks any coiled-coil forming sequence. It has homology similar to the tail domains of Myosin VII and XV.[22]

Myosin V

Myosin V is an unconventional myosin motor, which is processive as a

dimer and has a step size of 36 nm.[23] It translocates (walks) along actin filaments traveling towards the barbed end (+ end) of the filaments. Myosin V is involved in the transport of cargo (e.g. RNA, vesicles, organelles, mitochondria) from the center of the cell to the periphery, but has been furthermore shown to act like a dynamic tether, retaining vesicles and organelles in the actin-rich periphery of cells.[24][25] A recent single molecule in vitro reconstitution study on assembling actin filaments suggests that Myosin V travels farther on newly assembling (ADP-Pi rich) F-actin, while processive runlengths are shorter on older (ADP-rich) F-actin.[26]

A ribbon diagram of the Myosin V molecular motor[27] pseudo-colored to illustrate major subdomains. In the interest of visual clarity, important loops (which are often labeled separately in the literature) are not singled out. This perspective highlights the nucleotide-binding site and the separation of the U50 and L50 subdomains which form the actin-binding site cleft.

The Myosin V motor head can be subdivided into the following functional regions:[27]

  • Nucleotide-binding site - These elements together coordinate di-valent metal cations (usually magnesium) and catalyze hydrolysis:
    • Switch I - This contains a highly conserved SSR motif. Isomerizes in the presence of ATP.
    • Switch II - This is the Kinase-GTPase version of the
      Walker B motif
      DxxG. Isomerizes in the presence of ATP.
    • P-loop - This contains the
      Walker A motif
      GxxxxGK(S,T). This is the primary ATP binding site.

Myosin VI

State of myosin VI from PDB 2V26 before the power stroke [32]

Myosin VI is an unconventional myosin motor, which is primarily processive as a dimer, but also acts as a nonprocessive monomer. It walks along actin filaments, travelling towards the pointed end (- end) of the filaments.

endocytic vesicles into the cell.[34]

Myosin VII

Myosin VII is an unconventional myosin with two FERM domains in the tail region. It has an extended lever arm consisting of five calmodulin binding IQ motifs followed by a single alpha helix (SAH)[35] Myosin VII is required for phagocytosis in Dictyostelium discoideum, spermatogenesis in C. elegans and stereocilia formation in mice and zebrafish.[36]

Myosin VIII

Myosin VIII is a plant-specific myosin linked to cell division;[37] specifically, it is involved in regulating the flow of cytoplasm between cells[38] and in the localization of vesicles to the phragmoplast.[39]

Myosin IX

Myosin IX is a group of single-headed motor proteins. It was first shown to be minus-end directed,[40] but a later study showed that it is plus-end directed.[41] The movement mechanism for this myosin is poorly understood.

Myosin X

Myosin X is an unconventional myosin motor, which is functional as a

dimer. The dimerization of myosin X is thought to be antiparallel.[42] This behavior has not been observed in other myosins. In mammalian cells, the motor is found to localize to filopodia. Myosin X walks towards the barbed ends of filaments. Some research suggests it preferentially walks on bundles of actin, rather than single filaments.[43]
It is the first myosin motor found to exhibit this behavior.

Myosin XI

Myosin XI directs the movement of organelles such as

chloroplasts according to light intensity and the formation of stromules interconnecting different plastids. Myosin XI also plays a key role in polar root tip growth and is necessary for proper root hair elongation.[45] A specific Myosin XI found in Nicotiana tabacum was discovered to be the fastest known processive molecular motor, moving at 7μm/s in 35 nm steps along the actin filament.[46]

Myosin XII

Myosin XIII

Myosin XIV

This myosin group has been found in the Apicomplexa phylum.[47] The myosins localize to plasma membranes of the intracellular parasites and may then be involved in the cell invasion process.[48]

This myosin is also found in the ciliated protozoan Tetrahymena thermaphila. Known functions include: transporting phagosomes to the nucleus and perturbing the developmentally regulated elimination of the macronucleus during conjugation.

Myosin XV

Myosin XV is necessary for the development of the actin core structure of the non-motile stereocilia located in the inner ear. It is thought to be functional as a monomer.

Myosin XVI

Myosin XVII

Myosin XVIII

MYO18A A gene on chromosome 17q11.2 that encodes actin-based motor molecules with ATPase activity, which may be involved in maintaining stromal cell scaffolding required for maintaining intercellular contact.

Myosin XIX

Unconventional myosin XIX (Myo19) is a mitochondrial associated myosin motor.[49]

Genes in humans

Note that not all of these genes are active.

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.

Paramyosin

Paramyosin is a large, 93-115kDa

Insecta.[50] 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.

Paramyosins can be found in seafood. A recent computational study showed that following human intestinal digestion, paramyosins of common octopus, Humboldt squid, Japanese abalone, Japanese scallop, Mediterranean mussel, Pacific oyster, sea cucumber, and Whiteleg shrimp could release short peptides that inhibit the enzymatic activities of angiotensin converting enzyme and dipeptidyl peptidase.[52]

References

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Further reading

Additional images

  • Phase 1
    Phase 1
  • Phase 2
    Phase 2
  • Phase 3
    Phase 3
  • Phase 4
    Phase 4

External links

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