The kinetochore-bound Ska1 complex tracks depolymerizing microtubules and binds to curved protofilaments.

The kinetochore-bound Ska1 complex tracks depolymerizing microtubules and binds to curved protofilaments.
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DOI:
10.1016/j.devcel.2012.09.012
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发表时间:
2012-11-13
期刊:
影响因子:
11.8
通讯作者:
Cheeseman, Iain M.
Cheeseman, Iain M.
中科院分区:
生物学1区
文献类型:
--
作者:
Schmidt, Jens C.;Arthanari, Haribabu;Boeszoermenyi, Andras;Dashkevich, Natalia M.;Wilson-Kubalek, Elizabeth M.;Monnier, Nilah;Markus, Michelle;Oberer, Monika;Milligan, Ron A.;Bathe, Mark;Wagner, Gerhard;Grishchuk, Ekaterina L.;Cheeseman, Iain M.

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为了确保在有丝分裂过程中染色体分离相等,大分子动粒必须保持附着在解聚微管上,微管驱动染色体运动。动粒如何与解聚微管(微管经历戏剧性的结构变化形成弯曲的原丝)联系在一起,在脊椎动物中还没有被定义。在这里,我们证明了保守的kinetochore本地化Ska 1复杂的轨道解聚微管末端,并与微管晶格和弯曲的原丝。相比之下,Ndc 80复合物,一个中央球员在kinetochore-microtubule接口,绑定到直的微管晶格,缺乏跟踪活动。我们证明,Ska 1复杂赋予其跟踪能力的Ndc 80复杂。最后,我们提出了Ska 1微管结合域的结构,揭示了它与微管的相互作用和极光B的调节。这项工作定义了一个集成的kinetochore-microtubule接口形成的Ska 1和Ndc 80复合物,与解聚微管,可能通过与弯曲的微管原丝相互作用。
To ensure equal chromosome segregation during mitosis, the macromolecular kinetochore must remain attached to depolymerizing microtubules, which drive chromosome movements. How kinetochores associate with depolymerizing microtubules, which undergo dramatic structural changes forming curved protofilaments, has yet to be defined in vertebrates. Here, we demonstrate that the conserved kinetochore-localized Ska1 complex tracks with depolymerizing microtubule ends and associates with both the microtubule lattice and curved protofilaments. In contrast, the Ndc80 complex, a central player in the kinetochore-microtubule interface, binds only to the straight microtubule lattice and lacks tracking activity. We demonstrate that the Ska1 complex imparts its tracking capability to the Ndc80 complex. Finally, we present a structure of the Ska1 microtubule binding domain that reveals its interaction with microtubules and its regulation by Aurora B. This work defines an integrated kinetochore-microtubule interface formed by the Ska1 and Ndc80 complexes that associates with depolymerizing microtubules, potentially by interacting with curved microtubule protofilaments.
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