The structure of the myosin VI motor reveals the mechanism of directionality reversal
The structure of the myosin VI motor reveals the mechanism of directionality reversal
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DOI：
10.1038/nature03592
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发表时间：
2005-06-09
期刊：
影响因子：
64.8
通讯作者：
Houdusse, A
中科院分区：
文献类型：
--
作者：
Ménétrey, J;Bahloul, A;Houdusse, A
在这里，我们解决了反向肌球蛋白马达的截断版本的2.4埃结构，肌球蛋白VI，它包含了两个钙调蛋白分子的运动域和结合位点。除了两个独特的插入物外，该结构只显示出运动域与正端定向肌球蛋白的微小差异。第一个是在核苷酸结合口袋附近，改变核苷酸结合和解离的速率。第二个独特的插入物形成了肌球蛋白VI转换结构域的组成部分，以及与插入物内的新靶基序结合的钙调蛋白。这有助于将肌球蛋白VI的有效“杠杆臂”(包括与‘IQ基序’结合的第二个钙调蛋白)重定向到肌动蛋白细丝的尖端(负)。这种重新定位在很大程度上解释了这类肌球蛋白马达的反向。我们提出了一个模型，其中包含了一个类似Kinesin的解偶联/对接机制，以提供对Myosin VI运动的完整解释。
Here we solve a 2.4-angstrom structure of a truncated version of the reverse-direction myosin motor, myosin VI, that contains the motor domain and binding sites for two calmodulin molecules. The structure reveals only minor differences in the motor domain from that in plus-end directed myosins, with the exception of two unique inserts. The first is near the nucleotide-binding pocket and alters the rates of nucleotide association and dissociation. The second unique insert forms an integral part of the myosin VI converter domain along with a calmodulin bound to a novel target motif within the insert. This serves to redirect the effective 'lever arm' of myosin VI, which includes a second calmodulin bound to an 'IQ motif', towards the pointed ( minus) end of the actin filament. This repositioning largely accounts for the reverse directionality of this class of myosin motors. We propose a model incorporating a kinesin-like uncoupling/docking mechanism to provide a full explanation of the movements of myosin VI.