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着丝粒蛋白T上外动粒组装的分子基础

Molecular basis of outer kinetochore assembly on CENP-T.

作者信息

Huis In 't Veld Pim J, Jeganathan Sadasivam, Petrovic Arsen, Singh Priyanka, John Juliane, Krenn Veronica, Weissmann Florian, Bange Tanja, Musacchio Andrea

机构信息

Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Research Institute of Molecular Pathology (IMP), Vienna, Austria.

出版信息

Elife. 2016 Dec 24;5:e21007. doi: 10.7554/eLife.21007.

DOI:10.7554/eLife.21007
PMID:28012276
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5241120/
Abstract

Stable kinetochore-microtubule attachment is essential for cell division. It requires recruitment of outer kinetochore microtubule binders by centromere proteins C and T (CENP-C and CENP-T). To study the molecular requirements of kinetochore formation, we reconstituted the binding of the MIS12 and NDC80 outer kinetochore subcomplexes to CENP-C and CENP-T. Whereas CENP-C recruits a single MIS12:NDC80 complex, we show here that CENP-T binds one MIS12:NDC80 and two NDC80 complexes upon phosphorylation by the mitotic CDK1:Cyclin B complex at three distinct CENP-T sites. Visualization of reconstituted complexes by electron microscopy supports this model. Binding of CENP-C and CENP-T to MIS12 is competitive, and therefore CENP-C and CENP-T act in parallel to recruit two MIS12 and up to four NDC80 complexes. Our observations provide a molecular explanation for the stoichiometry of kinetochore components and its cell cycle regulation, and highlight how outer kinetochore modules bridge distances of well over 100 nm.

摘要

稳定的动粒-微管附着对于细胞分裂至关重要。它需要着丝粒蛋白C和T（CENP-C和CENP-T）招募外着丝粒微管结合蛋白。为了研究动粒形成的分子要求，我们重建了MIS12和NDC80外着丝粒亚复合物与CENP-C和CENP-T的结合。虽然CENP-C招募单个MIS12:NDC80复合物，但我们在此表明，有丝分裂CDK1:细胞周期蛋白B复合物在三个不同的CENP-T位点磷酸化后，CENP-T会结合一个MIS12:NDC80和两个NDC80复合物。通过电子显微镜观察重建的复合物支持了这一模型。CENP-C和CENP-T与MIS12的结合具有竞争性，因此CENP-C和CENP-T并行作用以招募两个MIS12和多达四个NDC80复合物。我们的观察结果为动粒组件的化学计量及其细胞周期调控提供了分子解释，并突出了外着丝粒模块如何跨越超过100纳米的距离。

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Insights from biochemical reconstitution into the architecture of human kinetochores.
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CENcyclopedia: Dynamic Landscape of Kinetochore Architecture Throughout the Cell Cycle.《细胞周期中动粒结构的动态全景百科全书》
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