4gb0

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{{STRUCTURE_4gb0| PDB=4gb0 | SCENE= }}
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==Crystal Structure of the RING domain of RNF168==
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===Crystal Structure of the RING domain of RNF168===
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<StructureSection load='4gb0' size='340' side='right' caption='[[4gb0]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23255131}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4gb0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GB0 FirstGlance]. <br>
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==Disease==
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNF168 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4gb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gb0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gb0 RCSB], [http://www.ebi.ac.uk/pdbsum/4gb0 PDBsum]</span></td></tr>
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</table>
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== Disease ==
[[http://www.uniprot.org/uniprot/RN168_HUMAN RN168_HUMAN]] Defects in RNF168 are the cause of Riddle syndrome (RIDDLES) [MIM:[http://omim.org/entry/611943 611943]]. Riddle syndrome is characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature. Defects are probably due to impaired localization of TP53BP1 and BRCA1 at DNA lesions.<ref>PMID:19203578</ref>
[[http://www.uniprot.org/uniprot/RN168_HUMAN RN168_HUMAN]] Defects in RNF168 are the cause of Riddle syndrome (RIDDLES) [MIM:[http://omim.org/entry/611943 611943]]. Riddle syndrome is characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature. Defects are probably due to impaired localization of TP53BP1 and BRCA1 at DNA lesions.<ref>PMID:19203578</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/RN168_HUMAN RN168_HUMAN]] E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).<ref>PMID:19203578</ref> <ref>PMID:19203579</ref> <ref>PMID:20550933</ref> <ref>PMID:22713238</ref> <ref>PMID:22373579</ref> <ref>PMID:22705371</ref> <ref>PMID:22742833</ref> <ref>PMID:22980979</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Ubiquitin adducts surrounding DNA double-strand breaks (DSBs) have emerged as molecular platforms important for the assembly of DNA damage mediator and repair proteins. Central to these chromatin modifications lies the E2 UBC13, which has been implicated in a bipartite role in priming and amplifying lys63-linked ubiquitin chains on histone molecules through coupling with the E3 RNF8 and RNF168. However, unlike the RNF8-UBC13 holoenyzme, exactly how RNF168 work in concert with UBC13 remains obscure. To provide a structural perspective for the RNF168-UBC13 complex, we solved the crystal structure of the RNF168 RING domain. Interestingly, while the RNF168 RING adopts a typical RING finger fold with two zinc ions coordinated by several conserved cystine and histine residues arranged in a C3HC4 "cross-brace" manner, structural superimposition of RNF168 RING with other UBC13-binding E3 ubiquitin ligases revealed substantial differences at its corresponding UBC13-binding interface. Consistently, and in stark contrast to that between RNF8 and UBC13, RNF168 did not stably associate with UBC13 in vitro or in vivo. Moreover, domain-swapping experiments indicated that the RNF8 and RNF168 RING domains are not functionally interchangeable. We propose that RNF8 and RNF168 operate in different modes with their cognate E2 UBC13 at DSBs.
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==Function==
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Structural basis for role of ring finger protein RNF168 RING domain.,Zhang X, Chen J, Wu M, Wu H, Arokiaraj AW, Wang C, Zhang W, Tao Y, Huen MS, Zang J Cell Cycle. 2013 Jan 15;12(2):312-21. doi: 10.4161/cc.23104. Epub 2012 Jan 15. PMID:23255131<ref>PMID:23255131</ref>
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[[http://www.uniprot.org/uniprot/RN168_HUMAN RN168_HUMAN]] E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).<ref>PMID:19203578</ref> <ref>PMID:19203579</ref> <ref>PMID:20550933</ref> <ref>PMID:22713238</ref> <ref>PMID:22373579</ref> <ref>PMID:22705371</ref> <ref>PMID:22742833</ref> <ref>PMID:22980979</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4gb0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GB0 OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:023255131</ref><references group="xtra"/><references/>
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*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Wang, C L.]]
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[[Category: Wang, C L]]
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[[Category: Zang, J Y.]]
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[[Category: Zang, J Y]]
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[[Category: Zhang, X Q.]]
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[[Category: Zhang, X Q]]
[[Category: E2]]
[[Category: E2]]
[[Category: E3 ligase]]
[[Category: E3 ligase]]
[[Category: Ligase]]
[[Category: Ligase]]
[[Category: Ring domain]]
[[Category: Ring domain]]

Revision as of 11:20, 20 January 2015

Crystal Structure of the RING domain of RNF168

4gb0, resolution 2.60Å

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