The central role of the tail in switching off 10S myosin II activity

被引:14
作者
Yang, Shixin [1 ]
Lee, Kyoung Hwan [1 ,3 ]
Woodhead, John L. [1 ]
Sato, Osamu [2 ]
Ikebe, Mitsuo [2 ]
Craig, Roger [1 ]
机构
[1] Univ Massachusetts, Med Sch, Dept Radiol, Div Cell Biol & Imaging, Worcester, MA 01605 USA
[2] Univ Texas Hlth Sci Ctr Tyler, Dept Cellular & Mol Biol, Tyler, TX USA
[3] Univ Massachusetts, Med Sch, Worcester, MA 01605 USA
基金
美国国家卫生研究院;
关键词
SMOOTH-MUSCLE MYOSIN; REGULATORY LIGHT-CHAIN; INTERACTING-HEADS MOTIF; HEAVY-MEROMYOSIN; STRIATED-MUSCLE; 3-DIMENSIONAL RECONSTRUCTION; MONOMERIC CONFORMATION; STRUCTURAL BASIS; RELAXED STATE; PHOSPHORYLATION;
D O I
10.1085/jgp.201912431
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Myosin II is a motor protein with two heads and an extended tail that plays an essential role in cell motility. Its active form is a polymer (myosin filament) that pulls on actin to generate motion. Its inactive form is a monomer with a compact structure (105 sedimentation coefficient), in which the tail is folded and the two heads interact with each other, inhibiting activity. This conformation is thought to function in cells as an energy-conserving form of the molecule suitable for storage as well as transport to sites of filament assembly. The mechanism of inhibition of the compact molecule is not fully understood. We have performed a 3-D reconstruction of negatively stained 105 myosin from smooth muscle in the inhibited state using single-particle analysis. The reconstruction reveals multiple interactions between the tail and the two heads that appear to trap ATP hydrolysis products, block actin binding, hinder head phosphorylation, and prevent filament formation. Blocking these essential features of myosin function could explain the high degree of inhibition of the folded form of myosin thought to underlie its energy-conserving function in cells. The reconstruction also suggests a mechanism for unfolding when myosin is activated by phosphorylation.
引用
收藏
页码:1081 / 1093
页数:13
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