期刊
CELL
卷 165, 期 6, 页码 1440-1453出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.05.037
关键词
-
资金
- Jane Coffin Childs, Leukemia & Lymphoma Society
- Edward R. & Anne G. Lefler Center
- CIHR
- Mitacs Elevate
- FWF-Hertha Firnberg Program
- Damon Runyon, Lallage Feazel Wall Fund
- Japan Society for the Promotion of Science
- CIHR MOP [111149, 136956]
- NIH [R01GM073960, R01GM026875, R01AG011085, R37GM065930, P30CA021765, P41GM103403]
- Boehringer Ingelheim
- Austrian Science Fund [SFB-F34]
- Austrian Research Promotion Agency (Headquarter grants) [FFG-832936, FFG-852936]
- European Community (FP7) [241548]
- DFG [Sonderforschungsbereich 860]
- ALSAC
- NECAT
- APS - NIH [P41GM103403]
- DOE [DE-AC02-06CH11357]
- Austrian Research Promotion Agency (Laura Bassi Centre for Optimized Structural Studies grant) [FFG-840283]
- HHMI
Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3-E2-substrate-UB architectures control different forms of polyubiquitination.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据