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| | + | '''Unreleased structure''' |
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| - | ==RAD51 filament on dsDNA bound by the BRCA2 c-terminus==
| + | The entry 8pbd is ON HOLD until Paper Publication |
| - | <StructureSection load='8pbd' size='340' side='right'caption='[[8pbd]], [[Resolution|resolution]] 2.83Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[8pbd]] is a 21 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=8PBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PBD 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">Electron Microscopy, [[Resolution|Resolution]] 2.83Å</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=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <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=8pbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pbd OCA], [https://pdbe.org/8pbd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pbd RCSB], [https://www.ebi.ac.uk/pdbsum/8pbd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pbd 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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| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
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| - | The BRCA2 tumour suppressor protein preserves genomic integrity via interactions with the DNA-strand exchange RAD51 protein in homology-directed repair. The RAD51-binding TR2 motif at the BRCA2 C-terminus is essential for protection and restart of stalled replication forks. Biochemical evidence shows that TR2 recognises filamentous RAD51, but existing models of TR2 binding to RAD51 lack a structural basis. Here we used cryo-electron microscopy and structure-guided mutagenesis to elucidate the mechanism of TR2 binding to nucleoprotein filaments of human RAD51. We find that TR2 binds across the protomer interface in the filament, acting as a brace for adjacent RAD51 molecules. TR2 targets an acidic-patch motif on human RAD51 that serves as a recruitment hub in fission yeast Rad51 for recombination mediators Rad52 and Rad55-Rad57. Our findings provide a structural rationale for RAD51 filament stabilisation by BRCA2 and reveal a common recruitment mechanism of recombination mediators to the RAD51 filament.
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| - | Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2.,Appleby R, Joudeh L, Cobbett K, Pellegrini L Nat Commun. 2023 Nov 2;14(1):7003. doi: 10.1038/s41467-023-42830-1. PMID:37919288<ref>PMID:37919288</ref>
| + | Authors: |
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | Description: |
| - | </div>
| + | [[Category: Unreleased Structures]] |
| - | <div class="pdbe-citations 8pbd" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: Homo sapiens]] | + | |
| - | [[Category: Large Structures]]
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| - | [[Category: Synthetic construct]]
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| - | [[Category: Appleby R]]
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| - | [[Category: Pellegrini L]]
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