5u6k
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of TopBP1 BRCT4/5 in complex with a BLM phosphopeptide== | |
| + | <StructureSection load='5u6k' size='340' side='right'caption='[[5u6k]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5u6k]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U6K 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]] 2.6Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=5u6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6k OCA], [https://pdbe.org/5u6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u6k RCSB], [https://www.ebi.ac.uk/pdbsum/5u6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6k ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TOPB1_MOUSE TOPB1_MOUSE] Required for DNA replication (By similarity). Plays a role in the rescue of stalled replication forks and checkpoint control (PubMed:14718568). Binds double-stranded DNA breaks and nicks as well as single-stranded DNA (By similarity). Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage (By similarity). Induces a large increase in the kinase activity of ATR (By similarity).[UniProtKB:Q92547]<ref>PMID:14718568</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Topoisomerase IIbeta binding protein 1 (TopBP1) is a critical protein-protein interaction hub in DNA replication checkpoint control. It was proposed that TopBP1 BRCT5 interacts with Bloom syndrome helicase (BLM) to regulate genome stability through either phospho-Ser304 or phospho-Ser338 of BLM. Here we show that TopBP1 BRCT5 specifically interacts with the BLM region surrounding pSer304, not pSer338. Our crystal structure of TopBP1 BRCT4/5 bound to BLM reveals recognition of pSer304 by a conserved pSer-binding pocket, and interactions between an FVPP motif N-terminal to pSer304 and a hydrophobic groove on BRCT5. This interaction utilizes the same surface of BRCT5 that recognizes the DNA damage mediator, MDC1; however the binding orientations of MDC1 and BLM are reversed. While the MDC1 interactions are largely electrostatic, the interaction with BLM has higher affinity and relies on a mix of electrostatics and hydrophobicity. We suggest that similar evolutionarily conserved interactions may govern interactions between TopBP1 and 53BP1. | ||
| - | + | Structural Insight into BLM Recognition by TopBP1.,Sun L, Huang Y, Edwards RA, Yang S, Blackford AN, Niedzwiedz W, Glover JNM Structure. 2017 Sep 1. pii: S0969-2126(17)30258-7. doi:, 10.1016/j.str.2017.08.005. PMID:28919440<ref>PMID:28919440</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5u6k" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Topoisomerase binding protein|Topoisomerase binding protein]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Edwards RA]] | ||
| + | [[Category: Glover JNM]] | ||
| + | [[Category: Sun L]] | ||
Current revision
Crystal structure of TopBP1 BRCT4/5 in complex with a BLM phosphopeptide
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