The central role of the tail in switching off 10S myosin II activity.
The central role of the tail in switching off 10S myosin II activity.
复制标题
尾部在关闭 10S 肌球蛋白 II 活性方面发挥着核心作用。
DOI：
10.1085/jgp.201912431
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Craig,Roger
中科院分区：
文献类型：
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作者：
Yang,Shixin;Lee,KyoungHwan;Woodhead,JohnL;Sato,Osamu;Ikebe,Mitsuo;Craig,Roger
肌球蛋白II是一种具有两个头部和一个延长的尾部的运动蛋白，在细胞运动中起着重要作用。它的活性形式是一种聚合物（肌球蛋白丝），可以拉动肌动蛋白产生运动。其非活性形式是具有紧凑结构（10 S沉降系数）的单体，其中尾部折叠，两个头部相互作用，抑制活性。这种构象被认为在细胞中作为一种节能形式的分子，适合于储存以及运输到细丝组装的位点。抑制致密分子的机制尚未完全了解。我们已经进行了3-D重建负染色的10 S肌球蛋白从平滑肌在抑制状态下使用单粒子分析。重建揭示了尾部和两个头部之间的多重相互作用，这些相互作用似乎可以捕获ATP水解产物，阻断肌动蛋白结合，阻碍头部磷酸化，并防止细丝形成。阻断肌球蛋白功能的这些基本特征可以解释肌球蛋白折叠形式的高度抑制，这种抑制被认为是其在细胞中能量保存功能的基础。重建也表明了肌球蛋白被磷酸化激活时展开的机制。
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 (10S 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 10S 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.