主轴检查点
后期促进复合物
动细胞
细胞生物学
CDC20型
有丝分裂
蛋白质亚单位
生物
主轴装置
化学
染色体分离
姐妹染色单体
德隆
后期
泛素连接酶
分子生物学
遗传学
泛素
细胞周期
细胞分裂
细胞
染色体
基因
作者
Claudio Alfieri,Leifu Chang,Ziguo Zhang,Jing Yang,Sarah Maslen,Mark Skehel,David Barford
出处
期刊:Nature
[Springer Nature]
日期:2016-08-01
卷期号:536 (7617): 431-436
被引量:176
摘要
In the dividing eukaryotic cell, the spindle assembly checkpoint (SAC) ensures that each daughter cell inherits an identical set of chromosomes. The SAC coordinates the correct attachment of sister chromatid kinetochores to the mitotic spindle with activation of the anaphase-promoting complex (APC/C), the E3 ubiquitin ligase responsible for initiating chromosome separation. In response to unattached kinetochores, the SAC generates the mitotic checkpoint complex (MCC), which inhibits the APC/C and delays chromosome segregation. By cryo-electron microscopy, here we determine the near-atomic resolution structure of a human APC/C–MCC complex (APC/C(MCC)). Degron-like sequences of the MCC subunit BubR1 block degron recognition sites on Cdc20, the APC/C coactivator subunit responsible for substrate interactions. BubR1 also obstructs binding of the initiating E2 enzyme UbcH10 to repress APC/C ubiquitination activity. Conformational variability of the complex enables UbcH10 association, and structural analysis shows how the Cdc20 subunit intrinsic to the MCC (Cdc20(MCC)) is ubiquitinated, a process that results in APC/C reactivation when the SAC is silenced.
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