Electron cryo-microscopy shows how strong binding of myosin to actin releases nucleotide
Electron cryo-microscopy shows how strong binding of myosin to actin releases nucleotide
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DOI：
10.1038/nature02005
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发表时间：
2003-09-25
期刊：
影响因子：
64.8
通讯作者：
Schröder, RR
中科院分区：
文献类型：
--
作者：
Holmes, KC;Angert, I;Schröder, RR
肌肉收缩涉及肌球蛋白横桥与肌动蛋白丝的周期性相互作用，这与三磷酸腺苷（ATP）水解的步骤相关联（1）。当每个横桥与肌动蛋白结合时，会发生一种构象变化，通常被称为“动力冲程”（2），它使肌动蛋白丝相对于肌球蛋白丝移动；这与ATP水解产物的释放以及肌球蛋白与肌动蛋白更强的结合相关。一个新的ATP分子的结合再次削弱这种结合，附着的横桥迅速从肌动蛋白上解离。然后核苷酸被水解，构象变化逆转，肌球蛋白横桥重新附着到肌动蛋白上。X射线晶体学已经确定了动力冲程的结构基础，但仍然不清楚为什么肌动蛋白的结合会削弱核苷酸的结合，反之亦然。在这里，我们通过将肌动蛋白和肌球蛋白横桥的原子模型拟合到高分辨率电子冷冻显微镜三维重建中，描述了这种联系的分子基础。当肌动蛋白结合时，肌动蛋白结合裂隙的闭合在结构上与核苷酸结合口袋的开启相关联。
Muscle contraction involves the cyclic interaction of the myosin cross-bridges with the actin filament, which is coupled to steps in the hydrolysis of ATP(1). While bound to actin each cross-bridge undergoes a conformational change, often referred to as the "power stroke"(2), which moves the actin filament past the myosin filaments; this is associated with the release of the products of ATP hydrolysis and a stronger binding of myosin to actin. The association of a new ATP molecule weakens the binding again, and the attached cross-bridge rapidly dissociates from actin. The nucleotide is then hydrolysed, the conformational change reverses, and the myosin cross-bridge reattaches to actin. X-ray crystallography has determined the structural basis of the power stroke, but it is still not clear why the binding of actin weakens that of the nucleotide and vice versa. Here we describe, by fitting atomic models of actin and the myosin cross-bridge into high-resolution electron cryo-microscopy three-dimensional reconstructions, the molecular basis of this linkage. The closing of the actin-binding cleft when actin binds is structurally coupled to the opening of the nucleotide-binding pocket.