4whv: Difference between revisions
New page: '''Unreleased structure''' The entry 4whv is ON HOLD Authors: Hodge, C.D., Edwards, R.A., Glover, J.N.M. Description: |
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The | ==E3 ubiquitin-protein ligase RNF8 in complex with Ubiquitin-conjugating enzyme E2 N and Polyubiquitin-B== | ||
<StructureSection load='4whv' size='340' side='right'caption='[[4whv]], [[Resolution|resolution]] 8.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4whv]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WHV FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 8.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4whv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4whv OCA], [https://pdbe.org/4whv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4whv RCSB], [https://www.ebi.ac.uk/pdbsum/4whv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4whv ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/UBE2N_HUMAN UBE2N_HUMAN] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).<ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:19269966</ref> <ref>PMID:20061386</ref> <ref>PMID:21512573</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
DNA double-strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone K63-linked ubiquitin chains in DSB signaling. Here we defined the activated RNF8/Ubc13~Ub complex by X-ray crystallography and its functional solution conformations by X-ray scattering, as tested by separation-of-function mutations imaged in cells by immunofluorescence. The collective results show that the RING E3 RNF8 targets E2 Ubc13 to DSB sites and plays a critical role in damage signaling by stimulating polyubiquitination through modulating conformations of ubiquitin covalently linked to the Ubc13 active site. Structure-guided separation-of-function mutations show that the RNF8 E2-stimulating activity is essential for DSB signaling in mammalian cells and necessary for downstream recruitment of 53BP1 and BRCA1. Chromatin targeted RNF168 rescues 53BP1 recruitment involved in non-homologous end joining, but not BRCA1 recruitment for homologous recombination. These findings suggest an allosteric approach to targeting the ubiquitin-docking cleft at the E2:E3 interface for possible interventions in cancer and chronic inflammation, and moreover establish an independent RNF8 role in BRCA1 recruitment. | |||
RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity that is Essential for DNA Double-Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment.,Hodge CD, Ismail IH, Edwards RA, Hura GL, Xiao AT, Tainer JA, Hendzel MJ, Glover JN J Biol Chem. 2016 Feb 22. pii: jbc.M116.715698. PMID:26903517<ref>PMID:26903517</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4whv" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] | |||
*[[3D structures of ubiquitin|3D structures of ubiquitin]] | |||
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Edwards RA]] | |||
[[Category: Glover JNM]] | |||
[[Category: Hodge CD]] | |||