KIF14 Binds Tightly to Microtubules and Adopts a Rigor-Like Conformation
KIF14 Binds Tightly to Microtubules and Adopts a Rigor-Like Conformation
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DOI：
10.1016/j.jmb.2014.05.030
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发表时间：
2014-08-26
影响因子：
5.6
通讯作者：
Kwok, Benjamin H.
中科院分区：
文献类型：
--
作者：
Arora, Kritica;Talje, Lama;Kwok, Benjamin H.
有丝分裂驱动蛋白马达蛋白KIF 14是细胞分裂期间胞质分裂所必需的，并且与脑发育和多种人类癌症有关。在这里，我们表明，小鼠KIF 14马达结构域紧密结合微管，并没有显示典型的核苷酸依赖性的变化，这种亲和力。它还具有强大的ATP酶活性，但运动非常缓慢。ADP结合形式的KIF 14马达结构域的晶体结构揭示了一个显着打开的ATP结合口袋，好像准备将其结合的ADP交换为Mg中心点ATP。在这种状态下，中央β-折叠的扭曲程度比在其他驱动蛋白中观察到的最大量高出10度。这种构型只在肌球蛋白的无核苷酸状态中出现，称为“类僵直”状态。从冷冻电子显微镜的电子密度图拟合这个原子模型表明一个独特的结合配置的电机域微管。我们假设KIF 14的这些特性非常适合于在胞质分裂期间稳定中间体微管。(C)2014作者出版社：Elsevier Ltd
The mitotic kinesin motor protein KIF14 is essential for cytokinesis during cell division and has been implicated in cerebral development and a variety of human cancers. Here we show that the mouse KIF14 motor domain binds tightly to microtubules and does not display typical nucleotide-dependent changes in this affinity. It also has robust ATPase activity but very slow motility. A crystal structure of the ADP-bound form of the KIF14 motor domain reveals a dramatically opened ATP-binding pocket, as if ready to exchange its bound ADP for Mg center dot ATP. In this state, the central beta-sheet is twisted similar to 10 degrees beyond the maximal amount observed in other kinesins. This configuration has only been seen in the nucleotide-free states of myosins-known as the "rigor-like" state. Fitting of this atomic model to electron density maps from cryo-electron microscopy indicates a distinct binding configuration of the motor domain to microtubules. We postulate that these properties of KIF14 are well suited for stabilizing midbody microtubules during cytokinesis. (C) 2014 The Authors. Published by Elsevier Ltd.