2azm

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{{Seed}}
 
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[[Image:2azm.png|left|200px]]
 
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==Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX==
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The line below this paragraph, containing "STRUCTURE_2azm", creates the "Structure Box" on the page.
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<StructureSection load='2azm' size='340' side='right'caption='[[2azm]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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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'>[[2azm]] 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=2AZM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AZM FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.41&#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=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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{{STRUCTURE_2azm| PDB=2azm | 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=2azm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2azm OCA], [https://pdbe.org/2azm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2azm RCSB], [https://www.ebi.ac.uk/pdbsum/2azm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2azm 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/az/2azm_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=2azm 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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Histone variant H2AX phosphorylation in response to DNA damage is the major signal for recruitment of DNA-damage-response proteins to regions of damaged chromatin. Loss of H2AX causes radiosensitivity, genome instability, and DNA double-strand-break repair defects, yet the mechanisms underlying these phenotypes remain obscure. Here, we demonstrate that mammalian MDC1/NFBD1 directly binds to phospho-H2AX (gammaH2AX) by specifically interacting with the phosphoepitope at the gammaH2AX carboxyl terminus. Moreover, through a combination of biochemical, cell-biological, and X-ray crystallographic approaches, we reveal the molecular details of the MDC1/NFBD1-gammaH2AX complex. These data provide compelling evidence that the MDC1/NFBD1 BRCT repeat domain is the major mediator of gammaH2AX recognition following DNA damage. We further show that MDC1/NFBD1-gammaH2AX complex formation regulates H2AX phosphorylation and is required for normal radioresistance and efficient accumulation of DNA-damage-response proteins on damaged chromatin. Thus, binding of MDC1/NFBD1 to gammaH2AX plays a central role in the mammalian response to DNA damage.
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===Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX===
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MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks.,Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP Cell. 2005 Dec 29;123(7):1213-26. PMID:16377563<ref>PMID:16377563</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>
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The line below this paragraph, {{ABSTRACT_PUBMED_16377563}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2azm" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 16377563 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16377563}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2AZM is a [[Single protein]] structure of sequence 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=2AZM OCA].
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==Reference==
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MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks., Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP, Cell. 2005 Dec 29;123(7):1213-26. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16377563 16377563]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Clapperton, J A.]]
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[[Category: Clapperton JA]]
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[[Category: Jackson, S P.]]
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[[Category: Jackson SP]]
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[[Category: Mohammad, D.]]
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[[Category: Mohammad D]]
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[[Category: Smerdon, S J.]]
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[[Category: Smerdon SJ]]
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[[Category: Stucki, M.]]
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[[Category: Stucki M]]
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[[Category: Yaffe, M B.]]
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[[Category: Yaffe MB]]
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[[Category: Brct repeat]]
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[[Category: Dna damage]]
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[[Category: Protein-phosphopeptide complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:14:36 2008''
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Current revision

Crystal structure of the MDC1 brct repeat in complex with the histone tail of gamma-H2AX

PDB ID 2azm

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