3k05

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{{Seed}}
 
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[[Image:3k05.jpg|left|200px]]
 
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==The crystal structure of MDC1 BRCT T2067D in complex with a minimal recognition tetrapeptide with an amidated C-terminus==
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The line below this paragraph, containing "STRUCTURE_3k05", creates the "Structure Box" on the page.
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<StructureSection load='3k05' size='340' side='right'caption='[[3k05]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3k05]] 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=3K05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K05 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.33&#8491;</td></tr>
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<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=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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{{STRUCTURE_3k05| PDB=3k05 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3k05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k05 OCA], [https://pdbe.org/3k05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k05 RCSB], [https://www.ebi.ac.uk/pdbsum/3k05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k05 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MDC1_HUMAN MDC1_HUMAN] Required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. May serve as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage marked by 'Ser-139' phosphorylation of histone H2AFX. Also required for downstream events subsequent to the recruitment of these proteins. These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1.<ref>PMID:14695167</ref> <ref>PMID:12475977</ref> <ref>PMID:12499369</ref> <ref>PMID:12551934</ref> <ref>PMID:12611903</ref> <ref>PMID:12607003</ref> <ref>PMID:12607004</ref> <ref>PMID:12607005</ref> <ref>PMID:15201865</ref> <ref>PMID:15377652</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k0/3k05_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=3k05 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The tandem BRCT domains of BRCA1 and MDC1 facilitate protein signaling at DNA damage foci through specific interactions with serine-phosphorylated protein partners. The MDC1 BRCT binds pSer-Gln-Glu-Tyr-COO(-) at the C terminus of the histone variant gammaH2AX via direct recognition of the C-terminal carboxylate, while BRCA1 recognizes pSer-X-X-Phe motifs either at C-terminal or internal sites within target proteins. Using fluorescence polarization binding assays, we show that while both BRCTs prefer a free main chain carboxylate at the +3 position, this preference is much more pronounced in MDC1. Crystal structures of BRCA1 and MDC1 bound to tetrapeptide substrates reveal differences in the environment of conserved arginines (Arg1699 in BRCA1 and Arg1933 in MDC1) that determine the relative affinity for peptides with -COO(-) versus -CO-NH(2) termini. A mutation in MDC1 that induces a more BRCA1-like conformation relaxes the binding specificity, allowing the mutant to bind phosphopeptides lacking a -COO(-) terminus.
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===The crystal structure of MDC1 BRCT T2067D in complex with a minimal recognition tetrapeptide with an amidated C-terminus===
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Comparison of the structures and peptide binding specificities of the BRCT domains of MDC1 and BRCA1.,Campbell SJ, Edwards RA, Glover JN Structure. 2010 Feb 10;18(2):167-76. PMID:20159462<ref>PMID:20159462</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3k05" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 20159462 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20159462}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3K05 is a 4 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K05 OCA].
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==Reference==
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<ref group="xtra">PMID:20159462</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Campbell, S J.]]
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[[Category: Large Structures]]
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[[Category: Alternative splicing]]
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[[Category: Campbell SJ]]
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[[Category: Brct domain]]
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[[Category: Edwards RA]]
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[[Category: Cell cycle]]
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[[Category: Glover JN]]
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[[Category: Dna damage]]
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[[Category: Dna damage response]]
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[[Category: Dna repair]]
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[[Category: H2ax]]
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[[Category: Nucleus]]
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[[Category: Phospho protein binding]]
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[[Category: Phosphoprotein]]
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[[Category: Polymorphism]]
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[[Category: Protein binding]]
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[[Category: Protein-peptide complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 3 16:35:22 2010''
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Current revision

The crystal structure of MDC1 BRCT T2067D in complex with a minimal recognition tetrapeptide with an amidated C-terminus

PDB ID 3k05

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