View source for 3uot


==Crystal Structure of MDC1 FHA Domain in Complex with a Phosphorylated Peptide from the MDC1 N-terminus==
<StructureSection load='3uot' size='340' side='right'caption='[[3uot]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3uot]] 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=3UOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UOT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<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=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=3uot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uot OCA], [https://pdbe.org/3uot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uot RCSB], [https://www.ebi.ac.uk/pdbsum/3uot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uot ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mdc1 is a large modular phosphoprotein scaffold that maintains signaling and repair complexes at double-stranded DNA break sites. Mdc1 is anchored to damaged chromatin through interaction of its C-terminal BRCT-repeat domain with the tail of gammaH2AX following DNA damage, but the role of the N-terminal forkhead-associated (FHA) domain remains unclear. We show that a major binding target of the Mdc1 FHA domain is a previously unidentified DNA damage and ATM-dependent phosphorylation site near the N-terminus of Mdc1 itself. Binding to this motif stabilizes a weak self-association of the FHA domain to form a tight dimer. X-ray structures of free and complexed Mdc1 FHA domain reveal a 'head-to-tail' dimerization mechanism that is closely related to that seen in pre-activated forms of the Chk2 DNA damage kinase, and which both positively and negatively influences Mdc1 FHA domain-mediated interactions in human cells prior to and following DNA damage.

The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator.,Jungmichel S, Clapperton JA, Lloyd J, Hari FJ, Spycher C, Pavic L, Li J, Haire LF, Bonalli M, Larsen DH, Lukas C, Lukas J, MacMillan D, Nielsen ML, Stucki M, Smerdon SJ Nucleic Acids Res. 2012 May;40(9):3913-28. Epub 2012 Jan 10. PMID:22234878<ref>PMID:22234878</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3uot" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Clapperton JA]]
[[Category: Haire LF]]
[[Category: Li J]]
[[Category: Lloyd J]]
[[Category: Smerdon SJ]]