Structure of myosin-1c tail bound to calmodulin provides insights into calcium-mediated conformational coupling
Structure of myosin-1c tail bound to calmodulin provides insights into calcium-mediated conformational coupling
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DOI：
10.1038/nsmb.2923
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发表时间：
2015-01-01
影响因子：
16.8
通讯作者：
Zhang, Mingjie
中科院分区：
文献类型：
--
作者：
Lu, Qing;Li, Jianchao;Zhang, Mingjie
I类肌球蛋白可以感知细胞的机械力，并作为张力敏感的锚或转运体发挥作用。在肌球蛋白-1中，机械负荷是如何从膜结合的尾部传递到力产生头部的尚不清楚。在这里，我们测定了小鼠肌球蛋白-1c的整个尾巴的晶体结构，表明肌球蛋白-1c采用了适合于力传导的稳定的单体构象。杠杆-臂螺旋和发动机的C-末端延伸的PH结构域通过一个稳定的后IQ结构域以一种非常不寻常的方式与钙调蛋白结合。钙离子与钙调蛋白结合可诱导IQ基序和IQ后结构域的主要构象变化，并增加肌球蛋白-1c尾部的灵活性。我们的研究为肌球蛋白-1的颈部和尾部结构域提供了结构蓝图，并扩展了主要的钙信号调节因子钙调蛋白的靶向结合模式。
Class I myosins can sense cellular mechanical forces and function as tension-sensitive anchors or transporters. How mechanical load is transduced from the membrane-binding tail to the force-generating head in myosin-1 is unknown. Here we determined the crystal structure of the entire tail of mouse myosin-1c in complex with apocalmodulin, showing that myosin-1c adopts a stable monomer conformation suited for force transduction. The lever-arm helix and the C-terminal extended PH domain of the motor are coupled by a stable post-IQ domain bound to calmodulin in a highly unusual mode. Ca2+ binding to calmodulin induces major conformational changes in both IQ motifs and the post-IQ domain and increases flexibility of the myosin-1c tail. Our study provides a structural blueprint for the neck and tail domains of myosin-1 and expands the target binding modes of the master Ca2+-signal regulator calmodulin.