研究提出myosin-2关闭状态的结构
2020-12-07   阅读:265   来源:自然

英国利兹大学Michelle Peckham研究组提出了肌球蛋白-2(myosin-2)关闭状态的结构。相关论文于2020年12月 2日发表于《自然》杂志。

他们报道了关闭的平滑肌肌球蛋白的冷冻电镜结构,其头部区域的分辨率为6Å。通过将晶体结构灵活地拟合到密度和分子动力学模拟中获得的伪原子模型描述了原子级的相互作用界面。一个调节性轻链的N末端延伸与尾巴相互作用,另一个与伴侣的头部相互作用,揭示了调节性轻链如何以不同方式稳定关闭状态,以及它们的磷酸化如何使肌球蛋白活化。

盘绕线圈的三个部分、马达结构域和轻链之间的其他相互作用使关闭状态稳定。每个头部中的杠杆结构可在激活时产生力。这种关闭结构与肌球蛋白2的所有同工型有关,并为了解其致病突变提供了框架。

研究人员表示,Myosin-2对于细胞分裂和肌肉收缩等各种过程至关重要。其调节性轻链的去磷酸化促进了不活跃的“关闭”状态,将形成细丝的尾部折叠到两个头部上,从而防止了细丝形成并使马达失活。发生这种情况的机制尚不清楚。

附:英文原文

Title: Structure of the shutdown state of myosin-2

Author: Charlotte A. Scarff, Glenn Carrington, David Casas-Mao, Joseph M. Chalovich, Peter J. Knight, Neil A. Ranson, Michelle Peckham

Issue&Volume: 2020-12-02

Abstract: Myosin-2 is essential for processes as diverse as cell division and muscle contraction. Dephosphorylation of its regulatory light chain promotes an inactive, ‘shutdown’ state with the filament-forming tail folded onto the two heads1, which prevents filament formation and inactivates the motors2. The mechanism by which this happens is unclear. Here we report a cryo-electron microscopy structure of shutdown smooth muscle myosin with a resolution of 6 in the head region. A pseudo-atomic model, obtained by flexible fitting of crystal structures into the density and molecular dynamics simulations, describes interaction interfaces at the atomic level. The N-terminal extension of one regulatory light chain interacts with the tail, and the other with the partner head, revealing how the regulatory light chains stabilize the shutdown state in different ways and how their phosphorylation would allow myosin activation. Additional interactions between the three segments of the coiled coil, the motor domains and the light chains stabilize the shutdown molecule. The structure of the lever in each head is competent to generate force upon activation. This shutdown structure is relevant to all isoforms of myosin-2 and provides a framework for understanding their disease-causing mutations.

DOI: 10.1038/s41586-020-2990-5

编辑:小柯机器人

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