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2jql

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Revision as of 07:20, 11 July 2018

NMR structure of the yeast Dun1 FHA domain in complex with a doubly phosphorylated (pT) peptide derived from Rad53 SCD1

Structural highlights

2jql is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	2jqi, 2jqj
Gene:	DUN1 (Saccharomyces cerevisiae)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DUN1_YEAST] Transducer of the DNA damage signal. Phosphorylates SML1 on serine residues. Cooperates with the PAN deadenylation complex in the regulation of RAD5 mRNA levels and cell survival in response to replicational stress.^[1] ^[2] [RAD53_YEAST] Controls S-phase checkpoint as well as G1 and G2 DNA damage checkpoints. Phosphorylates proteins on serine, threonine, and tyrosine. Prevents entry into anaphase and mitotic exit after DNA damage via regulation of the Polo kinase CDC5. Seems to be involved in the phosphorylation of RPH1.^[3] ^[4] ^[5] ^[6] ^[7]

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

Forkhead-associated (FHA) domains recognize phosphothreonines, and SQ/TQ cluster domains (SCDs) contain concentrated phosphorylation sites for ATM/ATR-like DNA-damage-response kinases. The Rad53-SCD1 has dual functions in regulating the activation of the Rad53-Dun1 checkpoint kinase cascade but with unknown molecular mechanisms. Here we present structural, biochemical, and genetic evidence that Dun1-FHA possesses an unprecedented diphosphothreonine-binding specificity. The Dun1-FHA has >100-fold increased affinity for diphosphorylated relative to monophosphorylated Rad53-SCD1 due to the presence of two separate phosphothreonine-binding pockets. In vivo, any single threonine of Rad53-SCD1 is sufficient for Rad53 activation and RAD53-dependent survival of DNA damage, but two adjacent phosphothreonines in the Rad53-SCD1 and two phosphothreonine-binding sites in the Dun1-FHA are necessary for Dun1 activation and DUN1-dependent transcriptional responses to DNA damage. The results uncover a phospho-counting mechanism that regulates the specificity of SCD, and provide mechanistic insight into a role of multisite phosphorylation in DNA-damage signaling.

Diphosphothreonine-specific interaction between an SQ/TQ cluster and an FHA domain in the Rad53-Dun1 kinase cascade.,Lee H, Yuan C, Hammet A, Mahajan A, Chen ES, Wu MR, Su MI, Heierhorst J, Tsai MD Mol Cell. 2008 Jun 20;30(6):767-78. PMID:18570878^[8]

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

References

↑ Hammet A, Pike BL, Heierhorst J. Posttranscriptional regulation of the RAD5 DNA repair gene by the Dun1 kinase and the Pan2-Pan3 poly(A)-nuclease complex contributes to survival of replication blocks. J Biol Chem. 2002 Jun 21;277(25):22469-74. Epub 2002 Apr 12. PMID:11953437 doi:http://dx.doi.org/10.1074/jbc.M202473200
↑ Zhao X, Rothstein R. The Dun1 checkpoint kinase phosphorylates and regulates the ribonucleotide reductase inhibitor Sml1. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3746-51. PMID:11904430 doi:http://dx.doi.org/10.1073/pnas.062502299
↑ Zheng P, Fay DS, Burton J, Xiao H, Pinkham JL, Stern DF. SPK1 is an essential S-phase-specific gene of Saccharomyces cerevisiae that encodes a nuclear serine/threonine/tyrosine kinase. Mol Cell Biol. 1993 Sep;13(9):5829-42. PMID:8355715
↑ Allen JB, Zhou Z, Siede W, Friedberg EC, Elledge SJ. The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. Genes Dev. 1994 Oct 15;8(20):2401-15. PMID:7958905
↑ Sanchez Y, Bachant J, Wang H, Hu F, Liu D, Tetzlaff M, Elledge SJ. Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science. 1999 Nov 5;286(5442):1166-71. PMID:10550056
↑ Kim EM, Jang YK, Park SD. Phosphorylation of Rph1, a damage-responsive repressor of PHR1 in Saccharomyces cerevisiae, is dependent upon Rad53 kinase. Nucleic Acids Res. 2002 Feb 1;30(3):643-8. PMID:11809875
↑ Pike BL, Yongkiettrakul S, Tsai MD, Heierhorst J. Mdt1, a novel Rad53 FHA1 domain-interacting protein, modulates DNA damage tolerance and G(2)/M cell cycle progression in Saccharomyces cerevisiae. Mol Cell Biol. 2004 Apr;24(7):2779-88. PMID:15024067
↑ Lee H, Yuan C, Hammet A, Mahajan A, Chen ES, Wu MR, Su MI, Heierhorst J, Tsai MD. Diphosphothreonine-specific interaction between an SQ/TQ cluster and an FHA domain in the Rad53-Dun1 kinase cascade. Mol Cell. 2008 Jun 20;30(6):767-78. PMID:18570878 doi:10.1016/j.molcel.2008.05.013

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2jql"

@@ Line 1: / Line 1: @@
 ==NMR structure of the yeast Dun1 FHA domain in complex with a doubly phosphorylated (pT) peptide derived from Rad53 SCD1==
 <StructureSection load='2jql' size='340' side='right' caption='[[2jql]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DUN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=2jql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jql OCA], [http://pdbe.org/2jql PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jql RCSB], [http://www.ebi.ac.uk/pdbsum/2jql 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=2jql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jql OCA], [http://pdbe.org/2jql PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jql RCSB], [http://www.ebi.ac.uk/pdbsum/2jql PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jql ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jq/2jql_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jq/2jql_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jql ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

2jql

From Proteopedia

Revision as of 07:20, 11 July 2018

NMR structure of the yeast Dun1 FHA domain in complex with a doubly phosphorylated (pT) peptide derived from Rad53 SCD1

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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