View source for 7zf1


==Structure of ubiquitinated FANCI in complex with FANCD2 and double-stranded DNA==
<StructureSection load='7zf1' size='340' side='right'caption='[[7zf1]], [[Resolution|resolution]] 4.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7zf1]] is a 5 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=7ZF1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZF1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.14&#8491;</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=7zf1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zf1 OCA], [https://pdbe.org/7zf1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zf1 RCSB], [https://www.ebi.ac.uk/pdbsum/7zf1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zf1 ProSAT]</span></td></tr>
</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> <ref>PMID:25862789</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Di-monoubiquitination of the FANCI-FANCD2 (ID2) complex is a central and crucial step for the repair of DNA interstrand crosslinks via the Fanconi anaemia pathway. While FANCD2 ubiquitination precedes FANCI ubiquitination, FANCD2 is also deubiquitinated at a faster rate than FANCI, which can result in a FANCI-ubiquitinated ID2 complex (I(Ub) D2). Here, we present a 4.1 A cryo-EM structure of I(Ub) D2 complex bound to double-stranded DNA. We show that this complex, like ID2(Ub) and I(Ub) D2(Ub) , is also in the closed ID2 conformation and clamps on DNA. The target lysine of FANCD2 (K561) becomes fully exposed in the I(Ub) D2-DNA structure and is thus primed for ubiquitination. Similarly, FANCI's target lysine (K523) is also primed for ubiquitination in the ID2(Ub) -DNA complex. The I(Ub) D2-DNA complex exhibits deubiquitination resistance, conferred by the presence of DNA and FANCD2. ID2(Ub) -DNA, on the other hand, can be efficiently deubiquitinated by USP1-UAF1, unless further ubiquitination on FANCI occurs. Therefore, FANCI ubiquitination effectively maintains FANCD2 ubiquitination in two ways: it prevents excessive FANCD2 deubiquitination within an I(Ub) D2(Ub) -DNA complex, and it enables re-ubiquitination of FANCD2 within a transient, closed-on-DNA, I(Ub) D2 complex.

Structural and biochemical basis of interdependent FANCI-FANCD2 ubiquitination.,Lemonidis K, Rennie ML, Arkinson C, Chaugule VK, Clarke M, Streetley J, Walden H EMBO J. 2023 Feb 1;42(3):e111898. doi: 10.15252/embj.2022111898. Epub 2022 Nov , 17. PMID:36385258<ref>PMID:36385258</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7zf1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Arkinson C]]
[[Category: Chaugule VK]]
[[Category: Clarke M]]
[[Category: Lemonidis K]]
[[Category: Rennie ML]]
[[Category: Streetley J]]
[[Category: Walden H]]