View source for 5nwl


==Crystal structure of a human RAD51-ATP filament.==
<StructureSection load='5nwl' size='340' side='right'caption='[[5nwl]], [[Resolution|resolution]] 3.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nwl]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NWL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NWL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.93&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5nwl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nwl OCA], [https://pdbe.org/5nwl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nwl RCSB], [https://www.ebi.ac.uk/pdbsum/5nwl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nwl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RAD51_HUMAN RAD51_HUMAN] Defects in RAD51 are a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.<ref>PMID:10807537</ref>   Defects in RAD51 are the cause of mirror movements type 2 (MRMV2) [MIM:[https://omim.org/entry/614508 614508]. A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities.<ref>PMID:22305526</ref> 
== Function ==
[https://www.uniprot.org/uniprot/RAD51_HUMAN RAD51_HUMAN] Participates in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Binds to single and double stranded DNA and exhibits DNA-dependent ATPase activity. Underwinds duplex DNA and forms helical nucleoprotein filaments. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3.<ref>PMID:18417535</ref> <ref>PMID:12205100</ref> <ref>PMID:20413593</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
An essential mechanism for repairing DNA double-strand breaks is homologous recombination (HR). One of its core catalysts is human RAD51 (hRAD51), which assembles as a helical nucleoprotein filament on single-stranded DNA, promoting DNA-strand exchange. Here, we study the interaction of hRAD51 with single-stranded DNA using a single-molecule approach. We show that ATP-bound hRAD51 filaments can exist in two different states with different contour lengths and with a free-energy difference of ~4 kBT per hRAD51 monomer. Upon ATP hydrolysis, the filaments convert into a disassembly-competent ADP-bound configuration. In agreement with the single-molecule analysis, we demonstrate the presence of two distinct protomer interfaces in the crystal structure of a hRAD51-ATP filament, providing a structural basis for the two conformational states of the filament. Together, our findings provide evidence that hRAD51-ATP filaments can exist in two interconvertible conformational states, which might be functionally relevant for DNA homology recognition and strand exchange.

Two distinct conformational states define the interaction of human RAD51-ATP with single-stranded DNA.,Brouwer I, Moschetti T, Candelli A, Garcin EB, Modesti M, Pellegrini L, Wuite GJ, Peterman EJ EMBO J. 2018 Apr 3;37(7). pii: embj.201798162. doi: 10.15252/embj.201798162. Epub, 2018 Mar 5. PMID:29507080<ref>PMID:29507080</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nwl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Moschetti T]]
[[Category: Pellegrini L]]