+Open data
-Basic information
Entry | Database: PDB / ID: 2mt5 | ||||||
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Title | Isolated Ring domain | ||||||
Components | Anaphase-promoting complex subunit 11 | ||||||
Keywords | METAL BINDING PROTEIN / Ring domain / zinc binding domain | ||||||
Function / homology | Function and homology information Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / anaphase-promoting complex-dependent catabolic process / regulation of meiotic cell cycle / positive regulation of mitotic metaphase/anaphase transition / Phosphorylation of the APC/C / protein K11-linked ubiquitination ...Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / anaphase-promoting complex-dependent catabolic process / regulation of meiotic cell cycle / positive regulation of mitotic metaphase/anaphase transition / Phosphorylation of the APC/C / protein K11-linked ubiquitination / ubiquitin-ubiquitin ligase activity / cullin family protein binding / Regulation of APC/C activators between G1/S and early anaphase / Transcriptional Regulation by VENTX / APC/C:Cdc20 mediated degradation of Cyclin B / regulation of mitotic cell cycle / APC-Cdc20 mediated degradation of Nek2A / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Assembly of the pre-replicative complex / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / CDK-mediated phosphorylation and removal of Cdc6 / Separation of Sister Chromatids / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / mitotic cell cycle / ubiquitin-dependent protein catabolic process / Senescence-Associated Secretory Phenotype (SASP) / protein ubiquitination / cell division / nucleolus / zinc ion binding / nucleoplasm / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | SOLUTION NMR / torsion angle dynamics | ||||||
Model details | lowest energy, model1 | ||||||
Authors | Brown, N.G. / Watson, E.R. / Weissman, F. / Royappa, G. / Schulman, B. / Jarvis, M. / Vanderlinden, R. / Frye, J.J. / Qiao, R. / Petzold, G. ...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. | ||||||
Citation | Journal: Mol Cell / Year: 2014 Title: Mechanism of polyubiquitination by human anaphase-promoting complex: RING repurposing for ubiquitin chain assembly. 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 ...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 / 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2mt5.cif.gz | 419.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2mt5.ent.gz | 350 KB | Display | PDB format |
PDBx/mmJSON format | 2mt5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mt/2mt5 ftp://data.pdbj.org/pub/pdb/validation_reports/mt/2mt5 | HTTPS FTP |
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-Related structure data
Related structure data | 2775C 6084C 4r2yC C: citing same article (ref.) |
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Similar structure data | |
Other databases |
-Links
-Assembly
Deposited unit |
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1 |
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NMR ensembles |
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-Components
#1: Protein | Mass: 8050.358 Da / Num. of mol.: 1 / Fragment: UNP residues 17-84 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC11, HSPC214 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9NYG5 |
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#2: Chemical |
-Experimental details
-Experiment
Experiment | Method: SOLUTION NMR Details: RING domain repurposing mechanism for 2-step polyubiquitination by the human APC | ||||||||||||||||||||||||||||
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NMR experiment |
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-Sample preparation
Details | Contents: 0.5 mM [U-100% 13C; U-100% 15N] protein_1, 90% H2O/10% D2O Solvent system: 90% H2O/10% D2O |
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Sample | Conc.: 0.5 mM / Component: entity_1-1 / Isotopic labeling: [U-100% 13C; U-100% 15N] |
Sample conditions | Ionic strength: 100 / pH: 7.0 / Pressure: ambient / Temperature: 298 K |
-NMR measurement
NMR spectrometer |
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-Processing
NMR software |
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Refinement | Method: torsion angle dynamics / Software ordinal: 1 | ||||||||||||||||
NMR constraints | NOE constraints total: 1033 / NOE intraresidue total count: 408 / NOE long range total count: 247 / NOE medium range total count: 118 / NOE sequential total count: 260 | ||||||||||||||||
NMR representative | Selection criteria: lowest energy | ||||||||||||||||
NMR ensemble | Conformer selection criteria: target function / Conformers calculated total number: 100 / Conformers submitted total number: 20 |