Cryo-EM reveals the structural basis of microtubule depolymerization by kinesin-13s.

Cryo-EM reveals the structural basis of microtubule depolymerization by kinesin-13s.
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DOI:
10.1038/s41467-018-04044-8
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发表时间:
2018-04-25
影响因子:
16.6
通讯作者:
Sosa H
Sosa H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Benoit MPMH;Asenjo AB;Sosa H

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驱动蛋白13s是驱动蛋白超家族中一个独特的组,它促进微管解聚,缺乏运动活性。驱动蛋白-13s解聚微管的分子机制,并适应于执行看似与其他驱动蛋白非常不同的活性,目前尚不清楚。为了解决这个问题,在这里,我们报告了在不同核苷酸状态下与弯曲或直小管蛋白结合的果蝇激酶-13 KLP10A蛋白结构的近原子分辨率冷冻电镜(cro - em)结构。这些结构显示了核苷酸在催化位点附近诱导的构象变化如何与激酶13特异性环-2的运动相结合,从而诱导微管曲率导致微管解聚。这些数据强调了一种模块化结构,这种结构允许类似的核心运动域用于不同的功能,例如运动性或微管解聚。驱动蛋白-13s是缺乏运动活性的微管解聚合酶。在这里,作者展示了不同核苷酸结合状态下酪蛋白-13微管复合物的低温电镜结构,揭示了ATP水解与构象变化的关系,并提出了酪蛋白诱导解聚合的模型。
Kinesin-13s constitute a distinct group within the kinesin superfamily of motor proteins that promote microtubule depolymerization and lack motile activity. The molecular mechanism by which kinesin-13s depolymerize microtubules and are adapted to perform a seemingly very different activity from other kinesins is still unclear. To address this issue, here we report the near atomic resolution cryo-electron microscopy (cryo-EM) structures of Drosophila melanogaster kinesin-13 KLP10A protein constructs bound to curved or straight tubulin in different nucleotide states. These structures show how nucleotide induced conformational changes near the catalytic site are coupled with movement of the kinesin-13-specific loop-2 to induce tubulin curvature leading to microtubule depolymerization. The data highlight a modular structure that allows similar kinesin core motor-domains to be used for different functions, such as motility or microtubule depolymerization. Kinesin-13s are microtubule depolymerases that lack motile activity. Here the authors present the cryo-EM structures of kinesin-13 microtubule complexes in different nucleotide bound states, which reveal how ATP hydrolysis is linked to conformational changes and propose a model for kinesin induced depolymerisation.
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