Unconventional myosin-VI, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is coded for by ''MYO6''.
Unconventional myosin-VI is a
myosin
Myosins () are a Protein family, family of motor proteins (though most often protein complexes) best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are adenosine triphosphate, ATP- ...
molecular motor involved in intracellular
vesicle
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
; In human embryology
* Vesicle (embryology), bulge-like features ...
and
organelle
In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...
transport.
Structure
Human myosin-VI contains a N-terminal
myosin head
The myosin head is the part of the thick myofilament made up of myosin that acts in muscle contraction, by sliding over thin myofilaments of actin. Myosin is the major component of the thick filaments and most myosin molecules are composed of a ...
domain (residues 59–759), two
coiled coil
A coiled coil is a structural motif in proteins in which two to seven alpha-helices are coiled together like the strands of a rope. ( Dimers and trimers are the most common types.) They have been found in roughly 5-10% of proteins and have a ...
motifs (residues 902–984 and 986–1009 respectively), and a C-terminal myosin VI cargo binding domain (residues 1177–1267).
Function
Unconventional myosin-VI is unique because it travels in the opposite direction of other myosins, towards the negative end of
actin filament
Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other p ...
s. Myosin-VI follows the same structure as other myosin but with two unique "inserts" allowing for its diversified properties. One insert is called the "reverse gear" and is responsible for its movement towards the negative end of actin filaments. The reverse gear is located on the neck region of the myosin and acts as a reorienting device for the lever arm to move backwards after myosin movement. The second insert assists in regulating
ATP enzyme activity located in the motor head domain.
There are 3 amino acid binding sites essential for myosin-VI's interactions, Arg-Arg-Leu and Trp-Trp-Tyr in the tail region and Met-Ile-Sec in the helix. The Arg-Arg-Leu amino acid segment (abbreviated RRL) takes part in ubiquitin interactions while Trp-Trp-Tyr (abbreviated WWY) assists in interactions with
DAB2. Myosin-VI's Met-Ile-Sec bonding interactions are limited to the myosin-VI long isoform but interact with clathrin in endocytosis.
Myosin-VI long isoform is formed by the inclusion of exon 31, adding an addition alpha-helix, restriction RRL interactions. Myosin-VI long struggles to interact with ubiquitin chains and GIPC1 due to this structural formation, however, increases attractivity to clathrin. Myosin-VI's structural flexibility provides a great width in interaction ability with its environment and interactors.
Interactions
MYO6 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with
GIPC1
GIPC PDZ domain containing family, member 1 (GIPC1) is a protein that in humans is encoded by the ''GIPC1'' gene. GIPC was originally identified as it binds specifically to the C terminus of RGS-GAIP, a protein involved in the regulation of G prot ...
,
DAB2.,
ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...
,
and
clathrin
Clathrin is a protein that plays a role in the formation of coated vesicles. Clathrin was first isolated by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskel ...
.
Myosin VI, being a motor protein, focuses its interactions by moving along actin filaments. This however does not limit its functions, because MYO6 is heavily involved in cytokinesis, creation of membrane compartments, and the regulation and organization of actin filaments.
Clinical significance
Mutations in the MYO6 gene are associated with hearing loss.
MYO6 has also been found to be involved in many events in
spermiogenesis
Spermiogenesis is the final stage of spermatogenesis, during which the spermatids develop into mature spermatozoon, spermatozoa. At the beginning of the stage, the spermatid is a more or less circular cell containing a cell nucleus, nucleus, Golg ...
in numerous different creatures. In common fruit flies (
Drosophila
''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...
), the myosin-VI ortholog controls the sterility of males by organization of actin involved in spermatid individualization. This same ortholog in roundworms (
C. elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' ( ...
) regulates the separation of cytosol in spermatid formation due to its influence in cytokinesis. In mice, this ortholog will control specialization and membrane compartment creation.
References
Further reading
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External links
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{{Cytoskeletal proteins