2n12
From Proteopedia
Solution structure of human Myosin VI isoform3 (1050-1131)
Structural highlights
DiseaseMYO6_HUMAN Autosomal dominant non-syndromic sensorineural deafness type DFNA;Autosomal recessive non-syndromic sensorineural deafness type DFNB;Progressive sensorineural hearing loss - hypertrophic cardiomyopathy. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionMYO6_HUMAN Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells (By similarity).[1] [2] [3] [4] Publication Abstract from PubMedMyosin VI functions in endocytosis and cell motility. Alternative splicing of myosin VI mRNA generates two distinct isoform types, myosin VIshort and myosin VIlong, which differ in the C-terminal region. Their physiological and pathological roles remain unknown. Here we identified an isoform-specific regulatory helix, named the alpha2-linker, that defines specific conformations and hence determines the target selectivity of human myosin VI. The presence of the alpha2-linker structurally defines a new clathrin-binding domain that is unique to myosin VIlong and masks the known RRL interaction motif. This finding is relevant to ovarian cancer, in which alternative myosin VI splicing is aberrantly regulated, and exon skipping dictates cell addiction to myosin VIshort in tumor-cell migration. The RRL interactor optineurin contributes to this process by selectively binding myosin VIshort. Thus, the alpha2-linker acts like a molecular switch that assigns myosin VI to distinct endocytic (myosin VIlong) or migratory (myosin VIshort) functional roles. Diverse functions of myosin VI elucidated by an isoform-specific alpha-helix domain.,Wollscheid HP, Biancospino M, He F, Magistrati E, Molteni E, Lupia M, Soffientini P, Rottner K, Cavallaro U, Pozzoli U, Mapelli M, Walters KJ, Polo S Nat Struct Mol Biol. 2016 Apr;23(4):300-8. doi: 10.1038/nsmb.3187. Epub 2016 Mar , 7. PMID:26950368[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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