PDBsum entry 2mt5

Metal binding protein

PDB id: 2mt5

Contents

Protein chain

70 a.a.

Metals

_ZN ×3

PDB id:

2mt5

Name:

Metal binding protein

Title:

Isolated ring domain

Structure:

Anaphase-promoting complex subunit 11. Chain: a. Fragment: unp residues 17-84. Synonym: apc11, cyclosome subunit 11, hepatocellular carcinoma- associated ring finger protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: anapc11, hspc214. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

N.G.Brown,E.R.Watson,F.Weissman,G.Royappa,B.Schulman,M.Jarvis, R.Vanderlinden,J.J.Frye,R.Qiao,G.Petzold,J.Peters,H.Stark

Key ref:

N.G.Brown et al. (2014). Mechanism of polyubiquitination by human anaphase-promoting complex: RING repurposing for ubiquitin chain assembly. Mol Cell, 56, 246-260. PubMed id: 25306923 DOI: 10.1016/j.molcel.2014.09.009

Date:

13-Aug-14 Release date: 29-Oct-14

Protein chain

Q9NYG5  (APC11_HUMAN) -  Anaphase-promoting complex subunit 11 from Homo sapiens

Seq: 84 a.a.

Struc: 70 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.molcel.2014.09.009

Mol Cell 56:246-260 (2014)

PubMed id: 25306923

Mechanism of polyubiquitination by human anaphase-promoting complex: RING repurposing for ubiquitin chain assembly.

N.G.Brown, E.R.Watson, F.Weissmann, M.A.Jarvis, R.VanderLinden, C.R.Grace, J.J.Frye, R.Qiao, P.Dube, G.Petzold, S.E.Cho, O.Alsharif, J.Bao, I.F.Davidson, J.J.Zheng, A.Nourse, I.Kurinov, J.M.Peters, H.Stark, B.A.Schulman.

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.