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1n0w

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[[Image:1n0w.gif|left|200px]]<br /><applet load="1n0w" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1n0w, resolution 1.70&Aring;" />
 
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'''Crystal structure of a RAD51-BRCA2 BRC repeat complex'''<br />
 
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==Overview==
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==Crystal structure of a RAD51-BRCA2 BRC repeat complex==
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The breast cancer susceptibility protein BRCA2 controls the function of RAD51, a recombinase enzyme, in pathways for DNA repair by homologous recombination. We report here the structure of a complex between an evolutionarily conserved sequence in BRCA2 (the BRC repeat) and the RecA-homology domain of RAD51. The BRC repeat mimics a motif in RAD51 that serves as an interface for oligomerization between individual RAD51 monomers, thus enabling BRCA2 to control the assembly of the RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. The RAD51 oligomerization motif is highly conserved among RecA-like recombinases, highlighting a common evolutionary origin for the mechanism of nucleoprotein filament formation, mirrored in the BRC repeat. Cancer-associated mutations that affect the BRC repeat disrupt its predicted interaction with RAD51, yielding structural insight into mechanisms for cancer susceptibility.
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<StructureSection load='1n0w' size='340' side='right'caption='[[1n0w]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1n0w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The April 2014 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''RecA and Rad51'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2014_4 10.2210/rcsb_pdb/mom_2014_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N0W 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]] 1.7&#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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=1n0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n0w OCA], [https://pdbe.org/1n0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n0w RCSB], [https://www.ebi.ac.uk/pdbsum/1n0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n0w ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n0/1n0w_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1n0w ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Breast cancer 2, early onset OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600185 600185]], Breast cancer, male, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600185 600185]], Breast cancer, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=179617 179617]], Fanconi anemia, complementation group D1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600185 600185]], Fanconi anemia, complementation group D2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227646 227646]], Pancreatic cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600185 600185]], Prostate cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600185 600185]], Wilms tumor OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600185 600185]]
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*[[BRCA 3D structures|BRCA 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1N0W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N0W OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Insights into DNA recombination from the structure of a RAD51-BRCA2 complex., Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, Venkitaraman AR, Nature. 2002 Nov 21;420(6913):287-93. Epub 2002 Nov 10. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12442171 12442171]
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[[Category: ]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Anand, S.]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Blundell, T L.]]
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[[Category: RecA and Rad51]]
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[[Category: Lee, M.]]
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[[Category: Anand S]]
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[[Category: Lo, T.]]
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[[Category: Blundell TL]]
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[[Category: Pellegrini, L.]]
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[[Category: Lee M]]
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[[Category: Venkitaraman, A R.]]
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[[Category: Lo T]]
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[[Category: Yu, D S.]]
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[[Category: Pellegrini L]]
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[[Category: CL]]
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[[Category: Venkitaraman AR]]
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[[Category: EDO]]
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[[Category: Yu DS]]
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[[Category: MG]]
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[[Category: breast cancer susceptibility]]
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[[Category: dna repair]]
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[[Category: homologous recombination]]
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[[Category: protein complex]]
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[[Category: reca-like atpase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:01:07 2008''
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Current revision

Crystal structure of a RAD51-BRCA2 BRC repeat complex

PDB ID 1n0w

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