Mechanism of polyubiquitination by human anaphase-promoting complex: RING repurposing for ubiquitin chain assembly
| Autor: | Prakash Dube, Jie Zheng, Jeremiah J. Frye, Renping Qiao, Holger Stark, Georg Petzold, Brenda A. Schulman, Marc A. Jarvis, Florian Weissmann, Ryan T. VanderLinden, Shein Ei Cho, Edmond R. Watson, Christy R. Grace, Amanda Nourse, Igor Kurinov, Ju Bao, Omar Alsharif, Jan-Michael Peters, Nicholas G. Brown, Iain F. Davidson |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cdc20 Proteins
macromolecular substances Ubiquitin-conjugating enzyme Ring (chemistry) Article Apc2 Subunit Anaphase-Promoting Complex-Cyclosome Protein structure Ubiquitin Humans Apc11 Subunit Anaphase-Promoting Complex-Cyclosome Polyubiquitin Peptide sequence Molecular Biology chemistry.chemical_classification DNA ligase biology Ubiquitination Cell Biology Cell biology Ubiquitin ligase Biochemistry chemistry Ubiquitin-Conjugating Enzymes biology.protein Peptide Biosynthesis Nucleic Acid-Independent Anaphase-promoting complex |
| Zdroj: | Molecular Cell |
| Popis: | 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 completely 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 unexpectedly diverse functions of RING E3s and E2s, and provide a framework for understanding distinctive RING E3 features specifying ubiquitin chain elongation. |
| Databáze: | OpenAIRE |
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