3T1N
Structure of human MICROCEPHALIN (MCPH1) TANDEM BRCT domains in complex with a CDC27 phosphopeptide
Summary for 3T1N
| Entry DOI | 10.2210/pdb3t1n/pdb |
| Descriptor | Microcephalin, Cdc27 peptide (3 entities in total) |
| Functional Keywords | tandem brct domains, cell cycle regulation, dna repair, mitosis, phosphorylation, cell cycle-peptide complex, cell cycle/peptide |
| Biological source | Homo sapiens (human) More |
| Cellular location | Cytoplasm, cytoskeleton, centrosome: Q8NEM0 |
| Total number of polymer chains | 4 |
| Total formula weight | 45052.00 |
| Authors | Singh, N.,Thompson, J.R.,Mer, G. (deposition date: 2011-07-22, release date: 2011-11-30, Last modification date: 2024-11-20) |
| Primary citation | Singh, N.,Wiltshire, T.D.,Thompson, J.R.,Mer, G.,Couch, F.J. Molecular Basis for the Association of Microcephalin (MCPH1) Protein with the Cell Division Cycle Protein 27 (Cdc27) Subunit of the Anaphase-promoting Complex. J.Biol.Chem., 287:2854-2862, 2012 Cited by PubMed Abstract: 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. Although 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 cell division cycle protein 27 (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 characterize this interaction further, 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. PubMed: 22139841DOI: 10.1074/jbc.M111.307868 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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