EMD-2775
Mechanism of polyubiquitination by human Anaphase Promoting Complex: RING repurposing for ubiquitin chain assembly
EMD-2775
Single-particle13.0 Å
Deposition: 02/09/2014Map released: 22/10/2014
Last modified: 19/11/2014
Sample Organism:
Homo sapiens
Sample: Anaphase Promoting Complex with bound Ube2S
Deposition Authors: Brown NG
,
Watson ER,
Weissmann F ,
Jarvis MA,
Vanderlinden R,
Grace CRR,
Frye JJ,
Qiao R,
Dube P,
Petzold G ,
Cho SE,
Alsharif O,
Bao J,
Davidson IF,
Zheng J,
Nourse A ,
Kurinov I,
Peters JM,
Stark H,
Schulman BA
Sample: Anaphase Promoting Complex with bound Ube2S
Deposition Authors: Brown NG
,
Watson ER,
Weissmann F ,
Jarvis MA,
Vanderlinden R,
Grace CRR,
Frye JJ,
Qiao R,
Dube P,
Petzold G ,
Cho SE,
Alsharif O,
Bao J,
Davidson IF,
Zheng J,
Nourse A ,
Kurinov I,
Peters JM,
Stark H,
Schulman BA
Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly.
Brown NG ,
Watson ER,
Weissmann F ,
Jarvis MA,
VanderLinden R,
Grace CR,
Frye JJ,
Qiao R,
Dube P,
Petzold G ,
Cho SE,
Alsharif O,
Bao J,
Davidson IF,
Zheng JJ ,
Nourse A ,
Kurinov I,
Peters JM,
Stark H,
Schulman BA
(2014) Mol. Cell , 56 , 246 - 260
,
Watson ER,
Weissmann F ,
Jarvis MA,
VanderLinden R,
Grace CR,
Frye JJ,
Qiao R,
Dube P,
Petzold G ,
Cho SE,
Alsharif O,
Bao J,
Davidson IF,
Zheng JJ ,
Nourse A ,
Kurinov I,
Peters JM,
Stark H,
Schulman BA
(2014) Mol. Cell , 56 , 246 - 260
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.
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.