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6rml

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Revision as of 06:54, 21 August 2019

Crystal structure of TOPBP1 BRCT0,1,2 in complex with a 53BP1 phosphopeptide

Structural highlights

6rml is a 3 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:
Gene:	TOPBP1, KIAA0259 (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

Coordination of the cellular response to DNA damage is organised by multi-domain 'scaffold' proteins, including 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ubiquitylation on other proteins, and are themselves carriers of such regulatory signals. Here we show that the DNA damage checkpoint regulating S-phase entry is controlled by a phosphorylation-dependent interaction of 53BP1 and TOPBP1. BRCT domains of TOPBP1 selectively bind conserved phosphorylation sites in the N-terminus of 53BP1. Mutation of these sites does not affect formation of 53BP1 or ATM foci following DNA damage, but abolishes recruitment of TOPBP1, ATR and CHK1 to 53BP1 damage foci, abrogating cell cycle arrest and permitting progression into S-phase. TOPBP1 interaction with 53BP1 is structurally complimentary to its interaction with RAD9-RAD1-HUS1, allowing these damage recognition factors to bind simultaneously to the same TOPBP1 molecule and cooperate in ATR activation in the G1 DNA damage checkpoint.

Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint.,Bigot N, Day M, Baldock RA, Watts FZ, Oliver AW, Pearl LH Elife. 2019 May 28;8. pii: 44353. doi: 10.7554/eLife.44353. PMID:31135337^[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
↑ Bigot N, Day M, Baldock RA, Watts FZ, Oliver AW, Pearl LH. Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint. Elife. 2019 May 28;8. pii: 44353. doi: 10.7554/eLife.44353. PMID:31135337 doi:http://dx.doi.org/10.7554/eLife.44353

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6rml"

@@ Line 3: / Line 3: @@
 <StructureSection load='6rml' size='340' side='right'caption='[[6rml]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6rml]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RML OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RML FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6rml]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RML OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RML FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TOPBP1, KIAA0259 ([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=6rml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rml OCA], [http://pdbe.org/6rml PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rml RCSB], [http://www.ebi.ac.uk/pdbsum/6rml PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rml ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Day, M]]

6rml

From Proteopedia

Revision as of 06:54, 21 August 2019

Crystal structure of TOPBP1 BRCT0,1,2 in complex with a 53BP1 phosphopeptide

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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