View source for 3sht


==Crystal structure of human MCPH1 tandem BRCT domains==
<StructureSection load='3sht' size='340' side='right'caption='[[3sht]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3sht]] is a 3 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=3SHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SHT 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]] 1.95&#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=3sht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sht OCA], [https://pdbe.org/3sht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sht RCSB], [https://www.ebi.ac.uk/pdbsum/3sht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sht ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MCPH1_HUMAN MCPH1_HUMAN] Premature chromosome condensation with microcephaly and intellectual deficit;Autosomal recessive primary microcephaly. Defects in MCPH1 are the cause of microcephaly primary type 1 (MCPH1) [MIM:[https://omim.org/entry/251200 251200]; also known as true microcephaly or microcephaly vera. Microcephaly is defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits. This entity is inherited as autosomal recessive trait.<ref>PMID:12046007</ref> <ref>PMID:15199523</ref> <ref>PMID:16211557</ref> 
== Function ==
[https://www.uniprot.org/uniprot/MCPH1_HUMAN MCPH1_HUMAN] Implicated in chromosome condensation and DNA damage induced cellular responses. May play a role in neurogenesis and regulation of the size of the cerebral cortex.<ref>PMID:12046007</ref> <ref>PMID:15199523</ref> <ref>PMID:15220350</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MCPH1 is especially important for linking chromatin remodeling to DNA damage response. It contains three BRCT (BRCA1-carboxyl terminal) domains. The N-terminal region directly binds with chromatin remodeling complex SWI-SNF, and the C-terminal BRCT2-BRCT3 domains (tandem BRCT domains) are involved in cellular DNA damage response. The MCPH1 gene associates with evolution of brain size, and its variation can cause primary microcephaly. In this study we solve the crystal structures of MCPH1 natural variant (A761) C-terminal tandem BRCT domains alone as well as in complex with gammaH2AX tail. Compared with other structures of tandem BRCT domains, the most significant differences lie in phosphopeptide binding pocket. Additionally, fluorescence polarization assays demonstrate that MCPH1 tandem BRCT domains show a binding selectivity on pSer +3 and prefer to bind phosphopeptide with free COOH-terminus. Taken together, our research provides new structural insights into BRCT-phosphopeptide recognition mechanism.

Specific recognition of phosphorylated tail of H2AX by the tandem BRCT domains of MCPH1 revealed by complex structure.,Shao Z, Li F, Sy SM, Yan W, Zhang Z, Gong D, Wen B, Huen MS, Gong Q, Wu J, Shi Y J Struct Biol. 2011 Dec 1. PMID:22154951<ref>PMID:22154951</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3sht" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li FD]]
[[Category: Shao ZH]]
[[Category: Yan W]]