期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 395, 期 5, 页码 908-915出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2009.11.029
关键词
microcephaly; Mcph1; BRCT domain; premature chromosome condensation; X-ray crystallography
资金
- Royal Society University Research Fellowship
- Cancer Research UK [C24461/A8032, C24461/A9549]
- Medical Research Council [G0800021]
- Career Development Faculty Programme of The Institute of Cancer Research
- Cancer Research UK for Structural Biology at ICR
- NHS
- National Institutes of Health
- Department of Defense
- MRC [G0800021] Funding Source: UKRI
- Medical Research Council [G0800021] Funding Source: researchfish
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 16 angstrom resolution Compared with other BRCT domain structures, the most striking differences are an elongated, ordered beta 1-alpha 1 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. (C) 2009 Elsevier Ltd. All rights reserved
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据