2N12

Solution structure of human Myosin VI isoform3 (1050-1131)

2N12 の概要

• エントリーDOI: 10.2210/pdb2n12/pdb
• 関連するPDBエントリー: 2N0Z 2N10 2N11 2N13 6E5N
• NMR情報: BMRB: 25544
• 分子名称: Unconventional myosin-VI (1 entity in total)
• 機能のキーワード: motor protein, protein transport
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein. Isoform 3: Cytoplasmic vesicle, clathrin- coated vesicle membrane. Isoform 4: Cytoplasmic vesicle, clathrin- coated vesicle membrane: Q9UM54
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9580.19

構造登録者

He, F.,Walters, K. (登録日: 2015-03-20, 公開日: 2016-03-02, 最終更新日: 2024-05-15)

主引用文献

Wollscheid, H.P.,Biancospino, M.,He, F.,Magistrati, E.,Molteni, E.,Lupia, M.,Soffientini, P.,Rottner, K.,Cavallaro, U.,Pozzoli, U.,Mapelli, M.,Walters, K.J.,Polo, S.
Diverse functions of myosin VI elucidated by an isoform-specific alpha-helix domain.
Nat.Struct.Mol.Biol., 23:300-308, 2016

PubMed Abstract: Myosin VI functions in endocytosis and cell motility. Alternative splicing of myosin VI mRNA generates two distinct isoform types, myosin VI(short) and myosin VI(long), which differ in the C-terminal region. Their physiological and pathological roles remain unknown. Here we identified an isoform-specific regulatory helix, named the α2-linker, that defines specific conformations and hence determines the target selectivity of human myosin VI. The presence of the α2-linker structurally defines a new clathrin-binding domain that is unique to myosin VI(long) 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 VI(short) in tumor-cell migration. The RRL interactor optineurin contributes to this process by selectively binding myosin VI(short). Thus, the α2-linker acts like a molecular switch that assigns myosin VI to distinct endocytic (myosin VI(long)) or migratory (myosin VI(short)) functional roles.

PubMed: 26950368
DOI: 10.1038/nsmb.3187

実験手法

SOLUTION NMR