2xnk: Difference between revisions

Latest revision as of 10:35, 20 December 2023

Structure and function of the Rad9-binding region of the DNA damage checkpoint adaptor TopBP1

Structural highlights

2xnk is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:	GOL, MSE
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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

TopBP1 is a scaffold protein that coordinates activation of the DNA-damage-checkpoint response by coupling binding of the 9-1-1 checkpoint clamp at sites of ssDNA, to activation of the ATR-ATRIP checkpoint kinase complex. We have now determined the crystal structure of the N-terminal region of human TopBP1, revealing an unexpected triple-BRCT domain structure. The arrangement of the BRCT domains differs significantly from previously described tandem BRCT domain structures, and presents two distinct sites for binding phosphopeptides in the second and third BRCT domains. We show that the site in the second but not third BRCT domain in the N-terminus of TopBP1, provides specific interaction with a phosphorylated motif at pSer387 in Rad9, which can be generated by CK2.

Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1.,Rappas M, Oliver AW, Pearl LH Nucleic Acids Res. 2010 Aug 20. PMID:20724438^[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
↑ Rappas M, Oliver AW, Pearl LH. Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1. Nucleic Acids Res. 2010 Aug 20. PMID:20724438 doi:10.1093/nar/gkq743

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] Rappas M, Oliver AW, Pearl LH. Structure and function of the Rad9-binding region of the DNA-damage checkpoint adaptor TopBP1. Nucleic Acids Res. 2010 Aug 20. PMID:20724438 doi:10.1093/nar/gkq743

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[5]

[6]

[7]

@@ Line 3: / Line 3: @@
 <StructureSection load='2xnk' size='340' side='right'caption='[[2xnk]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xnk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XNK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XNK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xnk]] is a 4 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=2XNK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XNK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1wf6|1wf6]], [[2xnh|2xnh]]</div></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=2xnk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xnk OCA], [https://pdbe.org/2xnk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xnk RCSB], [https://www.ebi.ac.uk/pdbsum/2xnk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xnk 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>
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Oliver, A W]]
+[[Category: Oliver AW]]
-[[Category: Pearl, L H]]
+[[Category: Pearl LH]]
-[[Category: Rappas, M]]
+[[Category: Rappas M]]
-[[Category: Dna repair]]
-[[Category: Isomerase]]
-[[Category: Phosphorylation]]
-[[Category: Protein-protein interaction]]

2xnk: Difference between revisions

Latest revision as of 10:35, 20 December 2023

Structure and function of the Rad9-binding region of the DNA damage checkpoint adaptor TopBP1

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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