2MT5

Isolated Ring domain

Summary for 2MT5

• Entry DOI: 10.2210/pdb2mt5/pdb
• NMR Information: BMRB: 25149
• Descriptor: Anaphase-promoting complex subunit 11, ZINC ION (2 entities in total)
• Functional Keywords: ring domain, zinc binding domain, metal binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q9NYG5
• Total number of polymer chains: 1
• Total formula weight: 8246.59

Authors

Brown, N.G.,Watson, E.R.,Weissman, F.,Royappa, G.,Schulman, B.,Jarvis, M.,Vanderlinden, R.,Frye, J.J.,Qiao, R.,Petzold, G.,Peters, J.,Stark, H. (deposition date: 2014-08-13, release date: 2014-10-29, Last modification date: 2024-05-15)

Primary citation

Brown, N.G.,Watson, E.R.,Weissmann, F.,Jarvis, M.A.,VanderLinden, R.,Grace, C.R.,Frye, J.J.,Qiao, R.,Dube, P.,Petzold, G.,Cho, S.E.,Alsharif, O.,Bao, J.,Davidson, I.F.,Zheng, J.J.,Nourse, A.,Kurinov, I.,Peters, J.M.,Stark, H.,Schulman, B.A.
Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly.
Mol.Cell, 56:246-260, 2014

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 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.

PubMed: 25306923
DOI: 10.1016/j.molcel.2014.09.009

Experimental method

SOLUTION NMR