2WT8

Structure of the N-terminal BRCT domain of human microcephalin (Mcph1)

Summary for 2WT8

• Entry DOI: 10.2210/pdb2wt8/pdb
• Descriptor: MICROCEPHALIN, ACETATE ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: cell cycle, chromosome condensation, dwarfism, polymorphism, microcephaly, phosphoprotein, mental retardation, primary microcephaly
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm, cytoskeleton, centrosome: Q8NEM0
• Total number of polymer chains: 4
• Total formula weight: 43425.58

Authors

Richards, M.W.,Roe, S.M.,Bayliss, R. (deposition date: 2009-09-14, release date: 2009-12-01, Last modification date: 2024-10-23)

Primary citation

Richards, M.W.,Leung, J.W.C.,Roe, S.M.,Chen, J.,Bayliss, R.
A Pocket on the Surface of the N-Terminal Brct Domain of Mcph1 is Required to Prevent Abnormal Chromosome Condensation.
J.Mol.Biol., 395:908-, 2010

PubMed Abstract: Mcph1 is mutated in autosomal recessive primary microcephaly and premature chromosome condensation (PCC) syndrome. Increased chromosome condensation is a common feature of cells isolated from patients afflicted with either disease. Normal cells depleted of Mcph1 also exhibit PCC phenotype. Human Mcph1 contains three BRCA1-carboxyl terminal (BRCT) domains, the first of which (Mcph1N) is necessary for the prevention of PCC. The only known disease-associated missense mutation in Mcph1 resides in this domain (T27R). We have determined the X-ray crystal structure of human Mcph1N to 1.6 A resolution. Compared with other BRCT domain structures, the most striking differences are an elongated, ordered beta1-alpha1 loop and an adjacent hydrophobic pocket. This pocket is in the equivalent structural position to the phosphate binding site of BRCT domains that recognize phospho-proteins, although the phosphate-binding residues are absent in Mcph1N. Mutations in the pocket abrogate the ability of full-length Mcph1 to rescue the PCC phenotype of Mcph1(-/-) mouse embryonic fibroblast cells, suggesting that it forms an essential part of a protein-protein interaction site necessary to prevent PCC.

PubMed: 19925808
DOI: 10.1016/J.JMB.2009.11.029

Experimental method

X-RAY DIFFRACTION (1.6 Å)