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美国马萨诸塞大学医学院Roger Craig研究小组解析出肌球蛋白II（10S）抑制形式的冷冻电镜结构。该项研究成果于2020年12月2日在线发表在《自然》杂志上。

通过具有足够分辨率的冷冻电镜，研究人员解析了平滑肌10S肌球蛋白的结构，从而能够更好地理解分子的头部和尾部区域的功能以及引起抑制作用的关键分子内接触。这项研究结果为了解肌球蛋白II的激活模式以及相关位点的致病机理提供了一种原子模型。

据介绍，肌球蛋白II是使肌肉细胞收缩和使非肌肉细胞移动并改变形状的运动蛋白。该分子的两个相同的头部连接在一条细长的尾巴上，可以两种构象存在：10S和6S，以其沉降系数命名。 6S构型具有延伸的尾巴，并组装成聚合物细丝，这些细丝拉动肌动蛋白丝以产生力和运动。在10S肌球蛋白中，尾巴被折叠成三段，头向后弯曲并彼此相互作用，尾巴形成一个紧凑的构象，其中ATPase活性、肌动蛋白激活和细丝组装都被高度抑制。

这种关闭的结构似乎在肌肉和非肌肉细胞中起着关键的能量存储作用，可以根据需要将其激活来形成功能性细丝，但是其抑制机理尚不清楚。

附：英文原文

Title: Cryo-EM structure of the inhibited (10S) form of myosin II

Author: Shixin Yang, Prince Tiwari, Kyoung Hwan Lee, Osamu Sato, Mitsuo Ikebe, Ral Padrn, Roger Craig

Issue&Volume: 2020-12-02

Abstract: Myosin II is the motor protein that enables muscle cells to contract and nonmuscle cells to move and change shape1. The molecule has two identical heads attached to an elongated tail, and can exist in two conformations: 10S and 6S, named for their sedimentation coefficients2,3. The 6S conformation has an extended tail and assembles into polymeric filaments, which pull on actin filaments to generate force and motion. In 10S myosin, the tail is folded into three segments and the heads bend back and interact with each other and the tail3,4,5,6,7, creating a compact conformation in which ATPase activity, actin activation and filament assembly are all highly inhibited7,8. This switched-off structure appears to function as a key energy-conserving storage molecule in muscle and nonmuscle cells9,10,11,12, which can be activated to form functional filaments as needed13—but the mechanism of its inhibition is not understood. Here we have solved the structure of smooth muscle 10S myosin by cryo-electron microscopy with sufficient resolution to enable improved understanding of the function of the head and tail regions of the molecule and of the key intramolecular contacts that cause inhibition. Our results suggest an atomic model for the off state of myosin II, for its activation and unfolding by phosphorylation, and for understanding the clustering of disease-causing mutations near sites of intramolecular interaction.

DOI: 10.1038/s41586-020-3007-0

Source: https://www.nature.com/articles/s41586-020-3007-0

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