- PDB-5jg6: APC11-Ubv shows role of noncovalent RING-Ubiquitin interactions i... -
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基本情報
登録情報
データベース: PDB / ID: 5jg6
タイトル
APC11-Ubv shows role of noncovalent RING-Ubiquitin interactions in processive multiubiquitination and Ubiquitin chain elongation by APC/C
要素
Anaphase-promoting complex subunit 11
Polyubiquitin-B
キーワード
CELL CYCLE / RING Ubiquitin Cell Cycle Anaphase-promoting complex-Cyclosome
機能・相同性
機能・相同性情報
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / protein branched polyubiquitination / regulation of meiotic cell cycle / anaphase-promoting complex-dependent catabolic process / Phosphorylation of the APC/C / positive regulation of mitotic metaphase/anaphase transition ...Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / protein branched polyubiquitination / regulation of meiotic cell cycle / anaphase-promoting complex-dependent catabolic process / Phosphorylation of the APC/C / positive regulation of mitotic metaphase/anaphase transition / protein K11-linked ubiquitination / symbiont entry into host cell via disruption of host cell glycocalyx / ubiquitin-ubiquitin ligase activity / symbiont entry into host cell via disruption of host cell envelope / virus tail / Regulation of APC/C activators between G1/S and early anaphase / cullin family protein binding / Transcriptional Regulation by VENTX / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / protein K48-linked ubiquitination / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / regulation of mitotic cell cycle / Assembly of the pre-replicative complex / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / CDK-mediated phosphorylation and removal of Cdc6 / G protein-coupled receptor binding / Separation of Sister Chromatids / Antigen processing: Ubiquitination & Proteasome degradation / ubiquitin protein ligase activity / mitotic cell cycle / Senescence-Associated Secretory Phenotype (SASP) / ubiquitin-dependent protein catabolic process / protein ubiquitination / cell division / nucleolus / zinc ion binding / nucleoplasm / nucleus / cytosol 類似検索 - 分子機能
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R37GM065930
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
P30CA021765
米国
St. Jude Children's Research Hospital (ALSAC)
米国
Howard Hughes Medical Institute (HHMI)
米国
Canadian Institutes of Health Research (CIHR)
MOP#111149
カナダ
Canadian Institutes of Health Research (CIHR)
136956
カナダ
Leukemia & Lymphoma Society
米国
Jane Coffin Childs Memorial Fund
米国
引用
ジャーナル: Cell / 年: 2016 タイトル: Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C. 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 / ...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 / 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.