肌球蛋白VI二聚化引发三螺旋束展开，以延长其作用范围。
Myosin VI dimerization triggers an unfolding of a three-helix bundle in order to extend its reach.
作者信息
Mukherjea Monalisa, Llinas Paola, Kim HyeongJun, Travaglia Mirko, Safer Daniel, Ménétrey Julie, Franzini-Armstrong Clara, Selvin Paul R, Houdusse Anne, Sweeney H Lee
机构信息
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
出版信息
Mol Cell. 2009 Aug 14;35(3):305-15. doi: 10.1016/j.molcel.2009.07.010. Epub 2009 Aug 6.
Myosin VI challenges the prevailing theory of how myosin motors move on actin: the lever arm hypothesis. While the reverse directionality and large powerstroke of myosin VI can be attributed to unusual properties of a subdomain of the motor (converter with a unique insert), these adaptations cannot account for the large step size on actin. Either the lever arm hypothesis needs modification, or myosin VI has some unique form of extension of its lever arm. We determined the structure of the region immediately distal to the lever arm of the motor and show that it is a three-helix bundle. Based on C-terminal truncations that display the normal range of step sizes on actin, CD, fluorescence studies, and a partial deletion of the bundle, we demonstrate that this bundle unfolds upon dimerization of two myosin VI monomers. This unconventional mechanism generates an extension of the lever arm of myosin VI.
肌球蛋白VI对肌球蛋白马达如何在肌动蛋白上移动的主流理论——杠杆臂假说提出了挑战。虽然肌球蛋白VI的反向运动性和大行程动力冲程可归因于马达一个亚结构域（带有独特插入片段的转换器）的异常特性，但这些适应性变化无法解释其在肌动蛋白上的大步长。要么杠杆臂假说需要修正，要么肌球蛋白VI具有某种独特的杠杆臂延伸形式。我们确定了马达杠杆臂紧邻区域的结构，并表明它是一个三螺旋束。基于在肌动蛋白上呈现正常步长范围的C端截短、圆二色性（CD）、荧光研究以及该束的部分缺失，我们证明这个束在两个肌球蛋白VI单体二聚化时会展开。这种非常规机制导致了肌球蛋白VI杠杆臂的延伸。
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