9-Angstrom Structure of a Microtubule-Bound Mitotic Motor
9-Angstrom Structure of a Microtubule-Bound Mitotic Motor
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DOI：
10.1016/j.jmb.2009.03.008
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发表时间：
2009-05-01
影响因子：
5.6
通讯作者：
Moores, Carolyn A.
中科院分区：
文献类型：
--
作者：
Bodey, Andrew J.;Kikkawa, Masahide;Moores, Carolyn A.
驱动蛋白-5（K5）马达是基于微管（MT）的细胞分裂机制的重要组成部分，也是目前癌症临床试验中小分子抑制剂的靶点。然而，K5-MT相互作用的性质和控制它的调节机制仍不清楚。使用低温电子显微镜和图像处理，我们计算了9 A分辨率下与MT结合的K5电机的结构，从而深入了解了这种重要的相互作用。我们的重建揭示了K5马达结构域的ATP样构象，其中MT结合诱导保守的核苷酸传感开关I和II环，形成一个紧凑的子域周围的绑定核苷酸。我们的重建还揭示了一种新的构象的K5特异性药物结合环5，这表明它在切换K5 s之间的力的产生和MT结合的扩散模式可能发挥的作用。因此，我们的数据揭示了重要的染色体分离纺锤体组件之间的相互作用的调节。(C)2009爱思唯尔有限公司保留所有权利。
Kinesin-5 (K5) motors are important components of the microtubule (MT)based cell division machinery and are targets for small-molecule inhibitors currently in cancer clinical trials. However, the nature of the K5-MT interaction and the regulatory mechanisms that control it remain unclear. Using cryo-electron microscopy and image processing, we calculated the structure of a K5 motor bound to MTs at 9 A resolution, providing insight into this important interaction. Our reconstruction reveals the K5 motor domain in an ATP-like conformation in which MT binding induces the conserved nucleotide-sensing switch I and II loops to form a compact subdomain around the bound nucleotide. Our reconstruction also reveals a novel conformation for the K5-specific drug-binding loop 5, suggesting a possible role for it in switching K5s between force generation and diffusional modes of MT binding. Our data thus shed light on regulation of the interaction between spindle components important for chromosome segregation. (C) 2009 Elsevier Ltd. All rights reserved.