2etx: Difference between revisions

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<StructureSection load='2etx' size='340' side='right'caption='[[2etx]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
<StructureSection load='2etx' size='340' side='right'caption='[[2etx]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2etx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ETX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ETX FirstGlance]. <br>
<table><tr><td colspan='2'>[[2etx]] is a 2 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=2ETX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ETX FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MDC1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
</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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2etx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2etx OCA], [https://pdbe.org/2etx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2etx RCSB], [https://www.ebi.ac.uk/pdbsum/2etx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2etx ProSAT]</span></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=2etx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2etx OCA], [https://pdbe.org/2etx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2etx RCSB], [https://www.ebi.ac.uk/pdbsum/2etx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2etx ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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>
[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>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=2etx 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=2etx ConSurf].
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== Publication Abstract from PubMed ==
Microcephalin (MCPH1), the first gene identified as causative for primary recessive autosomal microcephaly, is aberrantly expressed in autism-like disorders and human malignancy of breast and ovarian origin. MCPH1, the encoded protein product, has been implicated in various cellular processes including the DNA damage checkpoint, DNA repair and transcription. While our understanding of the cellular context in which MCPH1 operates continues to develop, a structural understanding of the C-terminal tandem BRCT domains of MCPH1 remains unexplored. Here, we identify Cdc27, a component of the anaphase-promoting complex (APC/C), as a novel interacting partner of MCPH1. We provide in vitro and in vivo evidence that the C-terminal tandem BRCT domains of MCPH1 (C-BRCTs) bind Cdc27 in a phosphorylation-dependent manner. To further characterize this interaction, we determined the structure of MCPH1 C-BRCTs in complex with a phosphorylated Cdc27 peptide (pCdc27) using X-ray crystallography. Based on this structure, we identified single amino acid mutations targeted at the binding interface that disrupted the MCPH1-pCdc27 interaction. Collectively, our data define the biochemical, structural and cellular determinants of the novel interaction between MCPH1 and Cdc27 and suggest that this interaction may occur within the larger context of MCPH1-APC/C.
Molecular basis for the association of microcephalin (MCPH1) with the cell division cycle protein 27 (Cdc27) subunit of the anaphase-promoting complex.,Singh N, Wiltshire T, Thompson JR, Mer G, Couch FJ J Biol Chem. 2011 Dec 2. PMID:22139841<ref>PMID:22139841</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2etx" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Joachimiak, A]]
[[Category: Joachimiak A]]
[[Category: Kim, Y]]
[[Category: Kim Y]]
[[Category: Mer, G]]
[[Category: Mer G]]
[[Category: Thompson, J R]]
[[Category: Thompson JR]]
[[Category: Wasielewski, E]]
[[Category: Wasielewski E]]
[[Category: Cell cycle]]
[[Category: Tandem brct domains histone gamma-h2ax]]

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