View source for 3ueo


==Crystal structure of TopBP1 BRCT4/5 domains in complex with a phospho-peptide==
<StructureSection load='3ueo' size='340' side='right'caption='[[3ueo]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ueo]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UEO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UEO 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]] 2.6&#8491;</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>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=3ueo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ueo OCA], [https://pdbe.org/3ueo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ueo RCSB], [https://www.ebi.ac.uk/pdbsum/3ueo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ueo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TOPB1_HUMAN TOPB1_HUMAN] Required for DNA replication. Plays a role in the rescue of stalled replication forks and checkpoint control. Binds double-stranded DNA breaks and nicks as well as single-stranded DNA. 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. Induces a large increase in the kinase activity of ATR.<ref>PMID:10498869</ref> <ref>PMID:11395493</ref> <ref>PMID:11714696</ref> <ref>PMID:12697828</ref> <ref>PMID:15075294</ref> <ref>PMID:16530042</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Activation of the DNA replication checkpoint by the ATR kinase requires protein interactions mediated by the ATR-activating protein, TopBP1. Accumulation of TopBP1 at stalled replication forks requires the interaction of TopBP1 BRCT5 with the phosphorylated SDT repeats of the adaptor protein MDC1. Here, we present the X-ray crystal structures of the tandem BRCT4/5 domains of TopBP1 free and in complex with a MDC1 consensus pSDpT phosphopeptide. TopBP1 BRCT4/5 adopts a variant BRCT-BRCT packing interface and recognizes its target peptide in a manner distinct from that observed in previous tandem BRCT- peptide structures. The phosphate-binding pocket and positively charged residues in a variant loop in BRCT5 present an extended binding surface for the negatively charged MDC1 phosphopeptide. Mutations in this surface reduce binding affinity and recruitment of TopBP1 to gammaH2AX foci in cells. These studies reveal a different mode of phosphopeptide binding by BRCT domains in the DNA damage response.

Structural insights into recognition of MDC1 by TopBP1 in DNA replication checkpoint control.,Leung CC, Sun L, Gong Z, Burkat M, Edwards R, Assmus M, Chen J, Glover JN Structure. 2013 Aug 6;21(8):1450-9. doi: 10.1016/j.str.2013.06.015. Epub 2013 Jul, 25. PMID:23891287<ref>PMID:23891287</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3ueo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Topoisomerase binding protein|Topoisomerase binding protein]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Glover JNM]]
[[Category: Leung CC]]