4bxo

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{{STRUCTURE_4bxo| PDB=4bxo | SCENE= }}
 
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===Architecture and DNA recognition elements of the Fanconi anemia FANCM- FAAP24 complex===
 
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{{ABSTRACT_PUBMED_23932590}}
 
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==Disease==
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==Architecture and DNA recognition elements of the Fanconi anemia FANCM- FAAP24 complex==
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[[http://www.uniprot.org/uniprot/FANCM_HUMAN FANCM_HUMAN]] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry.
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<StructureSection load='4bxo' size='340' side='right'caption='[[4bxo]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4bxo]] is a 4 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=4BXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BXO FirstGlance]. <br>
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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]] 2.15&#8491;</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=CA:CALCIUM+ION'>CA</scene></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=4bxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxo OCA], [https://pdbe.org/4bxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bxo RCSB], [https://www.ebi.ac.uk/pdbsum/4bxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bxo ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/FANCM_HUMAN FANCM_HUMAN] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/FANCM_HUMAN FANCM_HUMAN] ATPase required for FANCD2 ubiquitination, a key reaction in DNA repair. Binds to ssDNA but not to dsDNA. Recruited to forks stalled by DNA interstrand cross-links, and required for cellular resistance to such lesions.<ref>PMID:16116422</ref> <ref>PMID:16116434</ref> [REFERENCE:7][REFERENCE:8]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Fanconi anemia (FA) is a disorder associated with a failure in DNA repair. FANCM (defective in FA complementation group M) and its partner FAAP24 target other FA proteins to sites of DNA damage. FANCM-FAAP24 is related to XPF/MUS81 endonucleases but lacks endonucleolytic activity. We report a structure of an FANCM C-terminal fragment (FANCMCTD) bound to FAAP24 and DNA. This S-shaped structure reveals the FANCM (HhH)2 domain is buried, whereas the FAAP24 (HhH)2 domain engages DNA. We identify a second DNA contact and a metal center within the FANCM pseudo-nuclease domain and demonstrate that mutations in either region impair double-stranded DNA binding in vitro and FANCM-FAAP24 function in vivo. We show the FANCM translocase domain lies in proximity to FANCMCTD by electron microscopy and that binding fork DNA structures stimulate its ATPase activity. This suggests a tracking model for FANCM-FAAP24 until an encounter with a stalled replication fork triggers ATPase-mediated fork remodeling.
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==Function==
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Architecture and DNA Recognition Elements of the Fanconi Anemia FANCM-FAAP24 Complex.,Coulthard R, Deans AJ, Swuec P, Bowles M, Costa A, West SC, McDonald NQ Structure. 2013 Aug 6. pii: S0969-2126(13)00255-4. doi:, 10.1016/j.str.2013.07.006. PMID:23932590<ref>PMID:23932590</ref>
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[[http://www.uniprot.org/uniprot/FANCM_HUMAN FANCM_HUMAN]] ATPase required for FANCD2 ubiquitination, a key reaction in DNA repair. Binds to ssDNA but not to dsDNA. Recruited to forks stalled by DNA interstrand cross-links, and required for cellular resistance to such lesions.<ref>PMID:16116422</ref> <ref>PMID:16116434</ref> [REFERENCE:7][REFERENCE:8] [[http://www.uniprot.org/uniprot/FAP24_HUMAN FAP24_HUMAN]] Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. Regulates FANCD2 monoubiquitination upon DNA damage. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. Targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA.
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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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[[4bxo]] is a 4 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=4BXO OCA].
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</div>
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<div class="pdbe-citations 4bxo" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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<ref group="xtra">PMID:023932590</ref><references group="xtra"/><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: RNA helicase]]
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[[Category: Large Structures]]
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[[Category: Bowles, M.]]
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[[Category: Synthetic construct]]
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[[Category: Costa, A.]]
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[[Category: Bowles M]]
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[[Category: Coulthard, R.]]
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[[Category: Costa A]]
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[[Category: Deans, A.]]
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[[Category: Coulthard R]]
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[[Category: McDonald, N.]]
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[[Category: Deans A]]
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[[Category: Purkiss, A.]]
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[[Category: McDonald N]]
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[[Category: Swuec, P.]]
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[[Category: Purkiss A]]
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[[Category: West, S.]]
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[[Category: Swuec P]]
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[[Category: Dna binding]]
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[[Category: West S]]
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[[Category: Hydrolase-dna complex]]
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[[Category: Pseudo-nuclease]]
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Current revision

Architecture and DNA recognition elements of the Fanconi anemia FANCM- FAAP24 complex

PDB ID 4bxo

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