Atomic structure of the APC/C and its mechanism of protein ubiquitination | |
Article | |
关键词: ANAPHASE-PROMOTING COMPLEX; E3 LIGASE; CRYSTAL-STRUCTURE; CHAIN ELONGATION; CONJUGATING ENZYME; MITOTIC REGULATION; ACTIVATION; REVEALS; SUBUNIT; PHOSPHORYLATION; | |
DOI : 10.1038/nature14471 | |
来源: SCIE |
【 摘 要 】
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 early mitotic inhibitor 1 (Emi1) ensures the correct order and timing of distinct cell-cycle transitions. Here we use 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 future experiments to investigate APC/C functions in vivo.
【 授权许可】
Free