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3ueo

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Revision as of 16:36, 4 August 2016

Crystal structure of TopBP1 BRCT4/5 domains in complex with a phospho-peptide

Structural highlights

3ueo is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	,
Related:	3uen
Gene:	KIAA0259, TOPBP1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yamane K, Tsuruo T. Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA. Oncogene. 1999 Sep 16;18(37):5194-203. PMID:10498869 doi:10.1038/sj.onc.1202922
↑ Makiniemi M, Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Makela TP, Syvaoja JE. BRCT domain-containing protein TopBP1 functions in DNA replication and damage response. J Biol Chem. 2001 Aug 10;276(32):30399-406. Epub 2001 Jun 6. PMID:11395493 doi:10.1074/jbc.M102245200
↑ Honda Y, Tojo M, Matsuzaki K, Anan T, Matsumoto M, Ando M, Saya H, Nakao M. Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response. J Biol Chem. 2002 Feb 1;277(5):3599-605. Epub 2001 Nov 19. PMID:11714696 doi:10.1074/jbc.M104347200
↑ Liu K, Lin FT, Ruppert JM, Lin WC. Regulation of E2F1 by BRCT domain-containing protein TopBP1. Mol Cell Biol. 2003 May;23(9):3287-304. PMID:12697828
↑ Liu K, Luo Y, Lin FT, Lin WC. TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival. Genes Dev. 2004 Mar 15;18(6):673-86. PMID:15075294 doi:10.1101/gad.1180204
↑ Kumagai A, Lee J, Yoo HY, Dunphy WG. TopBP1 activates the ATR-ATRIP complex. Cell. 2006 Mar 10;124(5):943-55. PMID:16530042 doi:10.1016/j.cell.2005.12.041
↑ Leung CC, Sun L, Gong Z, Burkat M, Edwards R, Assmus M, Chen J, Glover JN. Structural insights into recognition of MDC1 by TopBP1 in DNA replication checkpoint control. Structure. 2013 Aug 6;21(8):1450-9. doi: 10.1016/j.str.2013.06.015. Epub 2013 Jul, 25. PMID:23891287 doi:http://dx.doi.org/10.1016/j.str.2013.06.015

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ueo"

@@ Line 1: / Line 1: @@
 ==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=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3uen|3uen]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIAA0259, TOPBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3ueo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ueo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ueo RCSB], [http://www.ebi.ac.uk/pdbsum/3ueo PDBsum]</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=3ueo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ueo OCA], [http://pdbe.org/3ueo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ueo RCSB], [http://www.ebi.ac.uk/pdbsum/3ueo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ueo ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 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==

3ueo

From Proteopedia

Revision as of 16:36, 4 August 2016

Crystal structure of TopBP1 BRCT4/5 domains in complex with a phospho-peptide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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