3t1n
From Proteopedia
(Difference between revisions)
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== Function == | == 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> | [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 == | ||
| + | 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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3t1n" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Structure of human MICROCEPHALIN (MCPH1) TANDEM BRCT domains in complex with a CDC27 phosphopeptide
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