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 nonmuscle cells. However, beginning in the 1970s, researchers began to discover new myosin genes in simple eukaryotes 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 (see phylogenetic tree). The unconventional myosins also have divergent tail domains, suggesting unique functions. 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
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 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. 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.
Myosin II of muscle contraction.
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. • 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, as in a
caduceus). Thus, myosin II has two heads. The intermediate
neck domain is the region creating the angle between the head and tail. In smooth muscle, a single gene (
MYH11)) codes for the heavy chains myosin II, but
splice variants of this gene result in four distinct isoforms. The movie begins with Myosin II in the 10S conformation with a folded tail domain, the blocked head and free head. The movie schematically depicts tail unfolding and the resulting active 6S confirmation followed by tail folding back to the 10S conformation. The illustration is conceptual: transitory states and diffusive motions associated with folding/unfolding are not shown.The MLC20 is also known as the
regulatory light chain and actively participates in
muscle contraction. 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 and may be in either auto-inhibited or active conformation. The balance/transition between active and inactive states is subject to extensive chemical regulation.
Myosin III Myosin III is a poorly understood member of the myosin family. It has been studied
in vivo in the eyes of
Drosophila, where it is thought to play a role in
phototransduction. A human
homologue gene for myosin III,
MYO3A, has been uncovered through the
Human Genome Project and is expressed in the
retina and
cochlea.
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.
Myosin V Myosin V is an unconventional myosin motor, which is processive as a
dimer and has a step size of 36 nm. 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. 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. -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. • Transducer - The seven
β-strands that underpin the motor head's structure. • U50 and L50 - The Upper (U50) and Lower (L50) domains are each around 50
kDa. Their spatial separation forms a cleft critical for binding to
actin and some regulatory compounds. • SH1 helix and Relay - These elements together provide an essential mechanism for coupling the enzymatic state of the motor domain to the powerstroke-producing region (converter domain, lever arm, and light chains). • Converter - This converts a change of conformation in the motor head to an angular displacement of the lever arm (in most cases reinforced with light chains). 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. 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 an extended lever arm consisting of five calmodulin binding IQ motifs followed by a single alpha helix (SAH) Myosin VII is required for
phagocytosis in
Dictyostelium discoideum,
spermatogenesis in
C. elegans and
stereocilia formation in mice and zebrafish.
Myosin VIII Myosin VIII is a plant-specific myosin linked to cell division; specifically, it is involved in regulating the flow of cytoplasm between cells and in the localization of vesicles to the
phragmoplast.
Myosin IX Myosin IX is a group of single-headed motor proteins. It was first shown to be minus-end directed, but a later study showed that it is plus-end directed. 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. 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. It is the first myosin motor found to exhibit this behavior.
Myosin XI Myosin XI directs the movement of organelles such as
plastids and
mitochondria in plant cells. It is responsible for the light-directed movement of
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. A specific Myosin XI found in
Nicotiana tabacum was discovered to be the fastest known processive
molecular motor, moving at 7 μm/s in 35 nm steps along the
actin filament.
Myosin XII Myosin XIII Myosin XIV This myosin group has been found in the
Apicomplexa phylum. The myosins localize to plasma membranes of the intracellular
parasites and may then be involved in the cell invasion process. This myosin is also found in the ciliated protozoan
Tetrahymena thermophila. 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. ==Genes in humans==