6vaa
From Proteopedia
(Difference between revisions)
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<StructureSection load='6vaa' size='340' side='right'caption='[[6vaa]], [[Resolution|resolution]] 3.35Å' scene=''> | <StructureSection load='6vaa' size='340' side='right'caption='[[6vaa]], [[Resolution|resolution]] 3.35Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6vaa]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VAA OCA]. For a <b>guided tour on the structure components</b> use [http:// | + | <table><tr><td colspan='2'>[[6vaa]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VAA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VAA FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FANCI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FANCD2, FACD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vaa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vaa OCA], [http://pdbe.org/6vaa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vaa RCSB], [http://www.ebi.ac.uk/pdbsum/6vaa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vaa ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/FACD2_HUMAN FACD2_HUMAN]] Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress. Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress. Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching.<ref>PMID:11239453</ref> <ref>PMID:11239454</ref> <ref>PMID:12086603</ref> <ref>PMID:12239151</ref> <ref>PMID:14517836</ref> <ref>PMID:15115758</ref> <ref>PMID:15314022</ref> <ref>PMID:15377654</ref> <ref>PMID:15454491</ref> <ref>PMID:15650050</ref> <ref>PMID:15661754</ref> <ref>PMID:15671039</ref> <ref>PMID:19465921</ref> | [[http://www.uniprot.org/uniprot/FACD2_HUMAN FACD2_HUMAN]] Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress. Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress. Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching.<ref>PMID:11239453</ref> <ref>PMID:11239454</ref> <ref>PMID:12086603</ref> <ref>PMID:12239151</ref> <ref>PMID:14517836</ref> <ref>PMID:15115758</ref> <ref>PMID:15314022</ref> <ref>PMID:15377654</ref> <ref>PMID:15454491</ref> <ref>PMID:15650050</ref> <ref>PMID:15661754</ref> <ref>PMID:15671039</ref> <ref>PMID:19465921</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The ID complex, involving the proteins FANCI and FANCD2, is required for the repair of DNA interstrand crosslinks (ICL) and related lesions(1). These proteins are mutated in Fanconi anaemia, a disease in which patients are predisposed to cancer. The Fanconi anaemia pathway of ICL repair is activated when a replication fork stalls at an ICL(2); this triggers monoubiquitination of the ID complex, in which one ubiquitin molecule is conjugated to each of FANCI and FANCD2. Monoubiquitination of ID is essential for ICL repair by excision, translesion synthesis and homologous recombination; however, its function remains unknown(1,3). Here we report a cryo-electron microscopy structure of the monoubiquitinated human ID complex bound to DNA, and reveal that it forms a closed ring that encircles the DNA. By comparison with the structure of the non-ubiquitinated ID complex bound to ICL DNA-which we also report here-we show that monoubiquitination triggers a complete rearrangement of the open, trough-like ID structure through the ubiquitin of one protomer binding to the other protomer in a reciprocal fashion. These structures-together with biochemical data-indicate that the monoubiquitinated ID complex loses its preference for ICL and related branched DNA structures, and becomes a sliding DNA clamp that can coordinate the subsequent repair reactions. Our findings also reveal how monoubiquitination in general can induce an alternative protein structure with a new function. | ||
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| + | DNA clamp function of the monoubiquitinated Fanconi anaemia ID complex.,Wang R, Wang S, Dhar A, Peralta C, Pavletich NP Nature. 2020 Apr;580(7802):278-282. doi: 10.1038/s41586-020-2110-6. Epub 2020 Mar, 11. PMID:32269332<ref>PMID:32269332</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6vaa" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Pavletich, N P]] | [[Category: Pavletich, N P]] | ||
Revision as of 06:11, 22 April 2020
Structure of the Fanconi Anemia ID complex bound to ICL DNA
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