Structural Motility, Institut Curie, Centre de Recherche, Paris, France.
Mol Cell. 2012 Oct 12;48(1):75-86. doi: 10.1016/j.molcel.2012.07.034. Epub 2012 Aug 30.
Myosin VI is the only known reverse-direction myosin motor. It has an unprecedented means of amplifying movements within the motor involving rearrangements of the converter subdomain at the C terminus of the motor and an unusual lever arm projecting from the converter. While the average step size of a myosin VI dimer is 30-36 nm, the step size is highly variable, presenting a challenge to the lever arm mechanism by which all myosins are thought to move. Herein, we present structures of myosin VI that reveal regions of compliance that allow an uncoupling of the lead head when movement is modeled on actin. The location of the compliance restricts the possible actin binding sites and predicts the observed stepping behavior. The model reveals that myosin VI, unlike plus-end directed myosins, does not use a pure lever arm mechanism, but instead steps with a mechanism analogous to the kinesin neck-linker uncoupling model.
肌球蛋白 VI 是唯一已知的反向运动肌球蛋白。它具有一种前所未有的放大运动的方式，涉及到马达 C 末端转换器亚基的重新排列，以及从转换器伸出的不寻常的杠杆臂。虽然肌球蛋白 VI 二聚体的平均步幅为 30-36nm，但步幅的变化很大，这对所有肌球蛋白被认为的运动的杠杆臂机制提出了挑战。在此，我们展示了肌球蛋白 VI 的结构，这些结构揭示了允许在肌动蛋白上模拟运动时，先导头部解耦的顺应性区域。顺应性的位置限制了可能的肌动蛋白结合位点，并预测了观察到的步进行为。该模型表明，肌球蛋白 VI 与正向肌球蛋白不同，它不使用纯杠杆臂机制，而是采用类似于驱动蛋白颈链接器解耦模型的机制进行步进。
