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==== | ==Cryo-EM structure of USP1-UAF1 bound to mono-ubiquitinated FANCD2, and FANCI== | ||
<StructureSection load='7ay1' size='340' side='right'caption='[[7ay1]]' scene=''> | <StructureSection load='7ay1' size='340' side='right'caption='[[7ay1]], [[Resolution|resolution]] 3.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ay1]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AY1 FirstGlance]. <br> | ||
</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=7ay1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ay1 OCA], [https://pdbe.org/7ay1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ay1 RCSB], [https://www.ebi.ac.uk/pdbsum/7ay1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ay1 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DN:UNKNOWN+2-DEOXYNUCLEOTIDE'>DN</scene>, <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=7ay1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ay1 OCA], [https://pdbe.org/7ay1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ay1 RCSB], [https://www.ebi.ac.uk/pdbsum/7ay1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ay1 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[[https://www.uniprot.org/uniprot/FANCI_HUMAN FANCI_HUMAN]] Fanconi anemia. The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | |||
[[https://www.uniprot.org/uniprot/FANCI_HUMAN FANCI_HUMAN]] Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA repair sites. Required for maintenance of chromosomal stability. Specifically binds branched DNA: binds both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Participates in S phase and G2 phase checkpoint activation upon DNA damage.<ref>PMID:17412408</ref> <ref>PMID:17452773</ref> <ref>PMID:17460694</ref> <ref>PMID:19111657</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Ubiquitin-specific protease 1 (USP1) acts together with the cofactor UAF1 during DNA repair processes to specifically remove monoubiquitin signals. One substrate of the USP1-UAF1 complex is the monoubiquitinated FANCI-FANCD2 heterodimer, which is involved in the repair of DNA interstrand crosslinks via the Fanconi anemia pathway. Here we determine structures of human USP1-UAF1 with and without ubiquitin and bound to monoubiquitinated FANCI-FANCD2. The crystal structures of USP1-UAF1 reveal plasticity in USP1 and key differences to USP12-UAF1 and USP46-UAF1, two related proteases. A cryo-EM reconstruction of USP1-UAF1 in complex with monoubiquitinated FANCI-FANCD2 highlights a highly orchestrated deubiquitination process, with USP1-UAF1 driving conformational changes in the substrate. An extensive interface between UAF1 and FANCI, confirmed by mutagenesis and biochemical assays, provides a molecular explanation for the requirement of both proteins, despite neither being directly involved in catalysis. Overall, our data provide molecular details of USP1-UAF1 regulation and substrate recognition. | |||
Structural basis of FANCD2 deubiquitination by USP1-UAF1.,Rennie ML, Arkinson C, Chaugule VK, Toth R, Walden H Nat Struct Mol Biol. 2021 Apr;28(4):356-364. doi: 10.1038/s41594-021-00576-8., Epub 2021 Apr 1. PMID:33795880<ref>PMID:33795880</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7ay1" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Thioesterase 3D structures|Thioesterase 3D structures]] | |||
*[[WD-repeat protein 3D structures|WD-repeat protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: Arkinson C]] | |||
[[Category: Rennie ML]] | |||
[[Category: Walden H]] | |||