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4orh

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==Crystal structure of RNF8 bound to the UBC13/MMS2 heterodimer==
==Crystal structure of RNF8 bound to the UBC13/MMS2 heterodimer==
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<StructureSection load='4orh' size='340' side='right' caption='[[4orh]], [[Resolution|resolution]] 4.80&Aring;' scene=''>
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<StructureSection load='4orh' size='340' side='right'caption='[[4orh]], [[Resolution|resolution]] 4.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4orh]] is a 11 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4epo 4epo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ORH FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4orh]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4epo 4epo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ORH FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.802&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMS2, UBE2V2, UEV2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBE2N, BLU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RNF8, KIAA0646 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4orh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orh OCA], [https://pdbe.org/4orh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4orh RCSB], [https://www.ebi.ac.uk/pdbsum/4orh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4orh ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4orh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4orh RCSB], [http://www.ebi.ac.uk/pdbsum/4orh PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/UB2V2_HUMAN UB2V2_HUMAN] Has no ubiquitin ligase activity on its own. The UBE2V2/UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination 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.<ref>PMID:9705497</ref> <ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:20061386</ref>
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The repair of DNA double strand breaks by homologous recombination relies on the unique topology of the chains formed by Lys-63 ubiquitylation of chromatin to recruit repair factors such as breast cancer 1 (BRCA1) to sites of DNA damage. The human RING finger (RNF) E3 ubiquitin ligases, RNF8 and RNF168, with the E2 ubiquitin-conjugating complex Ubc13/Mms2, perform the majority of Lys-63 ubiquitylation in homologous recombination. Here, we show that RNF8 dimerizes and binds to Ubc13/Mms2, thereby stimulating formation of Lys-63 ubiquitin chains, whereas the related RNF168 RING domain is a monomer and does not catalyze Lys-63 polyubiquitylation. The crystal structure of the RNF8/Ubc13/Mms2 ternary complex reveals the structural basis for the interaction between Ubc13 and the RNF8 RING and that an extended RNF8 coiled-coil is responsible for its dimerization. Mutations that disrupt the RNF8/Ubc13 binding surfaces, or that truncate the RNF8 coiled-coil, reduce RNF8-catalyzed ubiquitylation. These findings support the hypothesis that RNF8 is responsible for the initiation of Lys-63-linked ubiquitylation in the DNA damage response, which is subsequently amplified by RNF168.
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Molecular Insights into the Function of RING Finger (RNF)-containing Proteins hRNF8 and hRNF168 in Ubc13/Mms2-dependent Ubiquitylation.,Campbell SJ, Edwards RA, Leung CC, Neculai D, Hodge CD, Dhe-Paganon S, Glover JN J Biol Chem. 2012 Jul 6;287(28):23900-10. Epub 2012 May 15. PMID:22589545<ref>PMID:22589545</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]]
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*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
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*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
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*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Ubiquitin--protein ligase]]
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[[Category: Large Structures]]
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[[Category: Campbell, S J]]
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[[Category: Campbell SJ]]
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[[Category: Edwards, R A]]
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[[Category: Edwards RA]]
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[[Category: Glover, J N.M]]
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[[Category: Glover JNM]]
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[[Category: Coiled-coil]]
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[[Category: E3 ubiquitin ligase]]
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[[Category: Protein binding-ligase]]
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[[Category: Protein binding-ligase complex]]
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[[Category: Ubiquitin]]
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Current revision

Crystal structure of RNF8 bound to the UBC13/MMS2 heterodimer

PDB ID 4orh

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