The structure of the Ctf19c/CCAN from budding yeast
The structure of the Ctf19c/CCAN from budding yeast
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DOI：
10.7554/elife.44239
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发表时间：
2019-02-14
期刊：
影响因子：
7.7
通讯作者：
Harrison, Stephen C.
中科院分区：
文献类型：
--
作者：
Hinshaw, Stephen M.;Harrison, Stephen C.
真核生物的着丝点连接纺锤体微管和染色体着丝粒。酵母中一组叫做Ctf19复合物（Ctf19c）的蛋白质和其他生物体中的组成着丝粒相关网络（CCAN）构成着丝粒的基础。Ctf19c/CCAN影响着着丝粒组装的时间，通过与含有组蛋白H3变体Cse4/CENP-A的特殊核小体结合来确定其位置，并决定微管附着装置的组织。在这里，我们展示了一个重组的13亚基Ctf19c的结构，用类似于4埃分辨率的低温电子显微镜测定。该结构解释了已知的和推断的与Cse4核小体的接触以及观察到的组装层次结构。我们描述了它对着丝点的建立及其在整个细胞周期中由激酶调控的意义。
Eukaryotic kinetochores connect spindlemicrotubules to chromosomal centromeres. A group of proteins called the Ctf19 complex (Ctf19c) in yeast and the constitutive centromere associated network (CCAN) in other organisms creates the foundation of a kinetochore. The Ctf19c/CCAN influences the timing of kinetochore assembly, sets its location by associating with a specialized nucleosome containing the histone H3 variant Cse4/CENP-A, and determines the organization of the microtubule attachment apparatus. We present here the structure of a reconstituted 13-subunit Ctf19c determined by cryo-electron microscopy at similar to 4 angstrom resolution. The structure accounts for known and inferred contacts with the Cse4 nucleosome and for an observed assembly hierarchy. We describe its implications for establishment of kinetochores and for their regulation by kinases throughout the cell cycle.