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KIF14 binds tightly to microtubules and adopts a rigor-like conformation

机译:KIF14紧紧地绑定到微管,采用像严谨的构象

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摘要

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·ATP. In this state, the central β-sheet is twisted ~ 10° 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.
机译:有丝分裂的Kinesin Motor蛋白KIF14对于细胞分裂期间的细胞因子是必不可少的,并且涉及脑发育和各种人类癌症。在这里,我们显示小鼠KIF14电机结构域与微管粘合,并且不显示这种亲和力的典型核苷酸依赖性变化。它还具有稳健的ATP酶活性,但动力非常缓慢。 KIF14电机结构域的ADP绑定形式的晶体结构显示出显着打开的ATP结合口袋,仿佛准备好交换其结合的ADP·MG·ATP。在这种状态下,中央β-片材扭曲〜10°,超出在其他kinesins中观察到的最大量。在肌球蛋白的无核苷酸状态中才能看到这种配置 - 被称为“严谨性”状态。将该原子模型与来自冷冻电子显微镜的电子密度图的拟合表示电机结构域与微管的不同的结合配置。我们假设KIF14的这些性质非常适合于在细胞因子期间稳定仲体微管。

著录项

  • 来源
    《Journal of Molecular Biology》 |2014年第17期|共19页
  • 作者单位

    Department of Biomedical and Molecular Sciences Queen's University 18 Stuart St. Kingston ON;

    Institute for Research in Immunology and Cancer Département de Médecine Université de Montréal P;

    Department of Physiology and Biophysics Albert Einstein College of Medicine Bronx NY 10461;

    Institute for Research in Immunology and Cancer Département de Médecine Université de Montréal P;

    Institute for Research in Immunology and Cancer Département de Médecine Université de Montréal P;

    Department of Biomedical and Molecular Sciences Queen's University 18 Stuart St. Kingston ON;

    Department of Physiology and Biophysics Albert Einstein College of Medicine Bronx NY 10461;

    Department of Biomedical and Molecular Sciences Queen's University 18 Stuart St. Kingston ON;

    Institute for Research in Immunology and Cancer Département de Médecine Université de Montréal P;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
  • 关键词

    crystal structure; KIF14; kinesin; microtubules; motor protein;

    机译:晶体结构;KIF14;Kinesin;微管;电机蛋白质;

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