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Title | Mechanism of polyubiquitination by human anaphase-promoting complex: RING repurposing for ubiquitin chain assembly. |
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Journal, issue, pages | Mol Cell, Vol. 56, Issue 2, Page 246-260, Year 2014 |
Publish date | Oct 23, 2014 |
Authors | Nicholas G Brown / Edmond R Watson / Florian Weissmann / Marc A Jarvis / Ryan VanderLinden / Christy R R Grace / Jeremiah J Frye / Renping Qiao / Prakash Dube / Georg Petzold / Shein Ei Cho / Omar Alsharif / Ju Bao / Iain F Davidson / Jie J Zheng / Amanda Nourse / Igor Kurinov / Jan-Michael Peters / Holger Stark / Brenda A Schulman / |
PubMed Abstract | Polyubiquitination by E2 and E3 enzymes is a predominant mechanism regulating protein function. Some RING E3s, including anaphase-promoting complex/cyclosome (APC), catalyze polyubiquitination by ...Polyubiquitination by E2 and E3 enzymes is a predominant mechanism regulating protein function. Some RING E3s, including anaphase-promoting complex/cyclosome (APC), catalyze polyubiquitination by sequential reactions with two different E2s. An initiating E2 ligates ubiquitin to an E3-bound substrate. Another E2 grows a polyubiquitin chain on the ubiquitin-primed substrate through poorly defined mechanisms. Here we show that human APC's RING domain is repurposed for dual functions in polyubiquitination. The canonical RING surface activates an initiating E2-ubiquitin intermediate for substrate modification. However, APC engages and activates its specialized ubiquitin chain-elongating E2 UBE2S in ways that differ from current paradigms. During chain assembly, a distinct APC11 RING surface helps deliver a substrate-linked ubiquitin to accept another ubiquitin from UBE2S. Our data define mechanisms of APC/UBE2S-mediated polyubiquitination, reveal diverse functions of RING E3s and E2s, and provide a framework for understanding distinctive RING E3 features specifying ubiquitin chain elongation. |
External links | Mol Cell / PubMed:25306923 / PubMed Central |
Methods | EM (single particle) / NMR (solution) / X-ray diffraction |
Resolution | 1.755 - 23.0 Å |
Structure data | EMDB-2775: EMDB-6084: PDB-2mt5: PDB-4r2y: |
Chemicals | ChemComp-ZN: ChemComp-HOH: |
Source |
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Keywords | METAL BINDING PROTEIN / Ring domain / zinc binding domain / LIGASE / E3 Ubiquitin Ligase |