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-Structure paper
タイトル | Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C. |
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ジャーナル・号・ページ | Cell, Vol. 165, Issue 6, Page 1440-1453, Year 2016 |
掲載日 | 2016年6月2日 |
著者 | Nicholas G Brown / Ryan VanderLinden / Edmond R Watson / Florian Weissmann / Alban Ordureau / Kuen-Phon Wu / Wei Zhang / Shanshan Yu / Peter Y Mercredi / Joseph S Harrison / Iain F Davidson / Renping Qiao / Ying Lu / Prakash Dube / Michael R Brunner / Christy R R Grace / Darcie J Miller / David Haselbach / Marc A Jarvis / Masaya Yamaguchi / David Yanishevski / Georg Petzold / Sachdev S Sidhu / Brian Kuhlman / Marc W Kirschner / J Wade Harper / Jan-Michael Peters / Holger Stark / Brenda A Schulman / |
PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:27259151 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.0013 - 6.4 Å |
構造データ | EMDB-3432: Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2C (aka UBCH10)-substrate-Ubiquitin (variant) EMDB-3433: Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2S-Ubiquitin (variant)-substrate PDB-5jg6: |
化合物 | ChemComp-ZN: ChemComp-HOH: |
由来 |
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キーワード | CELL CYCLE / RING Ubiquitin Cell Cycle Anaphase-promoting complex-Cyclosome / Ubiquitination / multi-protein complex / cell division / conformational regulation / SIGNALING PROTEIN |