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Structure of Kif14: An engaging molecular motor

机译:Kif14的结构:一种引人入胜的分子马达

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Molecular motor proteins hydrolyze ATP to move unidirectionally along their partner filaments. Kinesin motors carry a variety of intracellular cargoes along microtubules. During mitosis, kinesins separate the two spindle poles [1,2], maintain kinetochore-microtubule attachments [3], and help to bundle microtubules in the central spindle that is required for cytokinesis [4]. While in solution, kinesins generally bind tightly to ADP and have low basal ATPase activity. Because of this, a pool of soluble motor can be maintained at the ready. This pool can be induced to bind microtubules and become activated by the release of autoinhibition [5-8], by phosphorylation [9], or by other means [10]. Several small molecule inhibitors of the mitotic kinesins Eg5 and CENP-E have been tested in Phase 1 and Phase 2 clinical trials as anticancer therapies [11]. These inhibitors lock the motors in a tightly ADP-bound solution state, preventing microtubule activation.
机译:分子运动蛋白水解ATP以使其伴侣细丝单向运动。驱动蛋白马达沿着微管携带多种细胞内货物。在有丝分裂期间,驱动蛋白将两个纺锤体极分开[1,2],保持动线体-微管附件[3],并帮助将微管束捆扎在胞质分裂所需的中心纺锤中[4]。在溶液中,驱动蛋白通常与ADP紧密结合,并具有较低的基础ATPase活性。因此,可以随时使用一台可溶性电动机。可以诱导该池结合微管并通过释放自抑制作用[5-8],通过磷酸化作用[9]或通过其他方式[10]激活。几种有丝分裂驱动蛋白Eg5和CENP-E的小分子抑制剂已在1期和2期临床试验中作为抗癌疗法进行了测试[11]。这些抑制剂可将电机锁定在与ADP紧密结合的溶液状态,从而防止微管激活。

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