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| - | [[Image:2kz3.jpg|left|200px]] | |
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| - | <!-- | + | ==Backbone 1H, 13C, and 15N Chemical Shift Assignments for human Rad51D from 1 to 83== |
| - | The line below this paragraph, containing "STRUCTURE_2kz3", creates the "Structure Box" on the page.
| + | <StructureSection load='2kz3' size='340' side='right'caption='[[2kz3]]' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | + | <table><tr><td colspan='2'>[[2kz3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KZ3 FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2kz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kz3 OCA], [https://pdbe.org/2kz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kz3 RCSB], [https://www.ebi.ac.uk/pdbsum/2kz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kz3 ProSAT]</span></td></tr> |
| - | {{STRUCTURE_2kz3| PDB=2kz3 | SCENE= }}
| + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/RA51D_HUMAN RA51D_HUMAN] Hereditary breast and ovarian cancer syndrome;Familial prostate cancer. Disease susceptibility is associated with variants affecting the gene represented in this entry. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/RA51D_HUMAN RA51D_HUMAN] Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Bind to single-stranded DNA (ssDNA) and has DNA-dependent ATPase activity. Part of the RAD51 paralog protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 binds predominantly to the intersection of the four duplex arms of the Holliday junction and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. Involved in telomere maintenance. The BCDX2 subcomplex XRCC2:RAD51D can stimulate Holliday junction resolution by BLM.<ref>PMID:10871607</ref> <ref>PMID:11751635</ref> <ref>PMID:11834724</ref> <ref>PMID:11842113</ref> <ref>PMID:12975363</ref> <ref>PMID:15109494</ref> <ref>PMID:23149936</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Rad51D, one of five Rad51 paralogs, is required for homologous recombination and disruption of Holliday junctions with bloom syndrome protein (BLM) in vertebrates. The N-terminal domain of Rad51D is highly conserved in eukaryotic Rad51D orthologs and is essential for protein-protein interaction with XRCC2, but nothing is known about its individual structure or function. In this study, we determined the solution structure of the human Rad51D N-terminal domain (residues 1-83), which consists of four short helices flanked by long N- and C-terminal tails. Interestingly, the position of the N-terminal tail (residues 1-13) is fixed within the domain structure via several hydrophobic interactions between Leu4 and Thr27, Leu4 and Val28, and Val6 and Ile17. We show that the domain preferentially binds to ssDNA versus dsDNA and does not bind to a mobile Holliday junction by electrophoretic mobility shift assay. NMR titration and dynamics studies showed that human Rad51D-N interacts with ssDNA by positively charged and hydrophobic residues on its surface. The results suggest that the N-terminal domain of Rad51D is required for the ssDNA-specific binding function of human Rad51D and that the conserved N-terminal domains of other Rad51 paralogs may have distinguishable functions from each other in homologous recombination. |
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| - | ===Backbone 1H, 13C, and 15N Chemical Shift Assignments for human Rad51D from 1 to 83===
| + | Structural and functional characterization of the N-terminal domain of human Rad51D.,Kim YM, Choi BS Int J Biochem Cell Biol. 2010 Nov 24. PMID:21111057<ref>PMID:21111057</ref> |
| | | | |
| - | | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | <!--
| + | </div> |
| - | The line below this paragraph, {{ABSTRACT_PUBMED_21111057}}, adds the Publication Abstract to the page
| + | <div class="pdbe-citations 2kz3" style="background-color:#fffaf0;"></div> |
| - | (as it appears on PubMed at http://www.pubmed.gov), where 21111057 is the PubMed ID number.
| + | == References == |
| - | -->
| + | <references/> |
| - | {{ABSTRACT_PUBMED_21111057}}
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==About this Structure== | + | |
| - | [[2kz3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KZ3 OCA].
| + | |
| - | | + | |
| - | ==Reference== | + | |
| - | <ref group="xtra">PMID:21111057</ref><references group="xtra"/> | + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Choi, N.]] | + | [[Category: Large Structures]] |
| - | [[Category: Kim, Y.]] | + | [[Category: Choi N]] |
| | + | [[Category: Kim Y]] |
| Structural highlights
Disease
RA51D_HUMAN Hereditary breast and ovarian cancer syndrome;Familial prostate cancer. Disease susceptibility is associated with variants affecting the gene represented in this entry.
Function
RA51D_HUMAN Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Bind to single-stranded DNA (ssDNA) and has DNA-dependent ATPase activity. Part of the RAD51 paralog protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 binds predominantly to the intersection of the four duplex arms of the Holliday junction and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. Involved in telomere maintenance. The BCDX2 subcomplex XRCC2:RAD51D can stimulate Holliday junction resolution by BLM.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
Rad51D, one of five Rad51 paralogs, is required for homologous recombination and disruption of Holliday junctions with bloom syndrome protein (BLM) in vertebrates. The N-terminal domain of Rad51D is highly conserved in eukaryotic Rad51D orthologs and is essential for protein-protein interaction with XRCC2, but nothing is known about its individual structure or function. In this study, we determined the solution structure of the human Rad51D N-terminal domain (residues 1-83), which consists of four short helices flanked by long N- and C-terminal tails. Interestingly, the position of the N-terminal tail (residues 1-13) is fixed within the domain structure via several hydrophobic interactions between Leu4 and Thr27, Leu4 and Val28, and Val6 and Ile17. We show that the domain preferentially binds to ssDNA versus dsDNA and does not bind to a mobile Holliday junction by electrophoretic mobility shift assay. NMR titration and dynamics studies showed that human Rad51D-N interacts with ssDNA by positively charged and hydrophobic residues on its surface. The results suggest that the N-terminal domain of Rad51D is required for the ssDNA-specific binding function of human Rad51D and that the conserved N-terminal domains of other Rad51 paralogs may have distinguishable functions from each other in homologous recombination.
Structural and functional characterization of the N-terminal domain of human Rad51D.,Kim YM, Choi BS Int J Biochem Cell Biol. 2010 Nov 24. PMID:21111057[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Braybrooke JP, Spink KG, Thacker J, Hickson ID. The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase that forms a complex with XRCC2. J Biol Chem. 2000 Sep 15;275(37):29100-6. PMID:10871607 doi:10.1074/jbc.M002075200
- ↑ Masson JY, Tarsounas MC, Stasiak AZ, Stasiak A, Shah R, McIlwraith MJ, Benson FE, West SC. Identification and purification of two distinct complexes containing the five RAD51 paralogs. Genes Dev. 2001 Dec 15;15(24):3296-307. PMID:11751635 doi:10.1101/gad.947001
- ↑ Kurumizaka H, Ikawa S, Nakada M, Enomoto R, Kagawa W, Kinebuchi T, Yamazoe M, Yokoyama S, Shibata T. Homologous pairing and ring and filament structure formation activities of the human Xrcc2*Rad51D complex. J Biol Chem. 2002 Apr 19;277(16):14315-20. PMID:11834724 doi:10.1074/jbc.M105719200
- ↑ Liu N, Schild D, Thelen MP, Thompson LH. Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in human cells. Nucleic Acids Res. 2002 Feb 15;30(4):1009-15. PMID:11842113 doi:10.1093/nar/30.4.1009
- ↑ Braybrooke JP, Li JL, Wu L, Caple F, Benson FE, Hickson ID. Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D). J Biol Chem. 2003 Nov 28;278(48):48357-66. PMID:12975363 doi:10.1074/jbc.M308838200
- ↑ Tarsounas M, Muñoz P, Claas A, Smiraldo PG, Pittman DL, Blasco MA, West SC. Telomere maintenance requires the RAD51D recombination/repair protein. Cell. 2004 Apr 30;117(3):337-47. PMID:15109494 doi:10.1016/s0092-8674(04)00337-x
- ↑ Chun J, Buechelmaier ES, Powell SN. Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway. Mol Cell Biol. 2013 Jan;33(2):387-95. PMID:23149936 doi:10.1128/MCB.00465-12
- ↑ Kim YM, Choi BS. Structural and functional characterization of the N-terminal domain of human Rad51D. Int J Biochem Cell Biol. 2010 Nov 24. PMID:21111057 doi:10.1016/j.biocel.2010.11.014
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