Atomic structure of the APC/C and its mechanism of protein ubiquitination.
Atomic structure of the APC/C and its mechanism of protein ubiquitination.
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DOI：
10.1038/nature14471
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发表时间：
2015-06-25
期刊：
影响因子：
64.8
通讯作者：
Barford D
中科院分区：
文献类型：
--
作者：
Chang L;Zhang Z;Yang J;McLaughlin SH;Barford D
后期促进复合物（APC/C）是一种多聚体RING E3泛素连接酶，控制染色体分离和有丝分裂退出。它的调节辅激活子亚基，磷酸化，有丝分裂检查点复合物，和间期抑制剂p53 - 1，确保正确的顺序和不同的细胞周期转换的时间。在这里，我们使用冷冻电子显微镜，以确定APC/C-辅激活因子复合物的原子结构，无论是EST 1或UbcH 10-泛素共轭。这些结构定义了所有APC/C亚基的结构，催化模块的位置，并解释了E2 s UbcH 10和Ube 2S是如何介导抑制的。Cdh 1与APC/C相互作用的定义表明它们如何被Cdh 1磷酸化拮抗。具有UbcH 10-泛素的APC/C的结构揭示了启动泛素化反应的见解。我们的结果为进一步研究体内APC/C功能的实验设计提供了定量框架。
The anaphase-promoting complex (APC/C) is a multimeric RING E3 ubiquitin ligase that controls chromosome segregation and mitotic exit. Its regulation by coactivator subunits, phosphorylation, the mitotic checkpoint complex, and interphase inhibitor Emi1 ensures the correct order and timing of distinct cell cycle transitions. Here, we used cryo-electron microscopy to determine atomic structures of APC/C-coactivator complexes with either Emi1 or a UbcH10-ubiquitin conjugate. These structures define the architecture of all APC/C subunits, the position of the catalytic module, and explain how Emi1 mediates inhibition of the two E2s UbcH10 and Ube2S. Definition of Cdh1 interactions with the APC/C indicates how they are antagonized by Cdh1 phosphorylation. The structure of the APC/C with UbcH10-ubiquitin reveals insights into the initiating ubiquitination reaction. Our results provide a quantitative framework for the design of experiments to further investigate APC/C functions in vivo.