6hm5
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of TOPBP1 BRCT0,1,2 in complex with a RAD9 phosphopeptide== | |
| + | <StructureSection load='6hm5' size='340' side='right' caption='[[6hm5]], [[Resolution|resolution]] 2.33Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6hm5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HM5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HM5 FirstGlance]. <br> | ||
| + | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Exodeoxyribonuclease_III Exodeoxyribonuclease III], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.11.2 3.1.11.2] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hm5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hm5 OCA], [http://pdbe.org/6hm5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hm5 RCSB], [http://www.ebi.ac.uk/pdbsum/6hm5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hm5 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/RAD9A_HUMAN RAD9A_HUMAN]] Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase. RAD9A possesses 3'->5' double stranded DNA exonuclease activity. Its phosphorylation by PRKCD may be required for the formation of the 9-1-1 complex.<ref>PMID:10713044</ref> <ref>PMID:21659603</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | TOPBP1 and its fission yeast homologueRad4, are critical players in a range of DNA replication, repair and damage signalling processes. They are composed of multiple BRCT domains, some of which bind phosphorylated motifs in other proteins. They thus act as multi-point adaptors bringing proteins together into functional combinations, dependent on post-translational modifications downstream of cell cycle and DNA damage signals. We have now structurally and/or biochemically characterised a sufficient number of high-affinity complexes for the conserved N-terminal region of TOPBP1 and Rad4 with diverse phospho-ligands, including human RAD9 and Treslin, and Schizosaccharomyces pombe Crb2 and Sld3, to define the determinants of BRCT domain specificity. We use this to identify and characterise previously unknown phosphorylation-dependent TOPBP1/Rad4-binding motifs in human RHNO1 and the fission yeast homologue of MDC1, Mdb1. These results provide important insights into how multiple BRCT domains within TOPBP1/Rad4 achieve selective and combinatorial binding of their multiple partner proteins. | ||
| - | + | BRCT domains of the DNA damage checkpoint proteins TOPBP1/Rad4 display distinct specificities for phosphopeptide ligands.,Day M, Rappas M, Ptasinska K, Boos D, Oliver AW, Pearl LH Elife. 2018 Oct 8;7. pii: 39979. doi: 10.7554/eLife.39979. PMID:30295604<ref>PMID:30295604</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6hm5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Exodeoxyribonuclease III]] | ||
[[Category: Day, M]] | [[Category: Day, M]] | ||
| - | [[Category: Oliver, A | + | [[Category: Oliver, A W]] |
| + | [[Category: Pearl, L H]] | ||
[[Category: Rappas, M]] | [[Category: Rappas, M]] | ||
| - | [[Category: | + | [[Category: Brct domain phosphopeptide recognition]] |
| + | [[Category: Cell cycle]] | ||
Current revision
Crystal structure of TOPBP1 BRCT0,1,2 in complex with a RAD9 phosphopeptide
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