View source for 2jqi


==NMR Structure of the Rad53 FHA1 domain in complex with a phosphothreonien peptide derived from Rad53 SCD1==
<StructureSection load='2jqi' size='340' side='right'caption='[[2jqi]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jqi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JQI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JQI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=2jqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jqi OCA], [https://pdbe.org/2jqi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jqi RCSB], [https://www.ebi.ac.uk/pdbsum/2jqi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jqi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RAD53_YEAST 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.<ref>PMID:8355715</ref> <ref>PMID:7958905</ref> <ref>PMID:10550056</ref> <ref>PMID:11809875</ref> <ref>PMID:15024067</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jq/2jqi_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=2jqi ConSurf].
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== 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 &gt;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<ref>PMID:18570878</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2jqi" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein kinase Spk1|Protein kinase Spk1]]
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Mahajan A]]
[[Category: Tsai M]]
[[Category: Yuan C]]