Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA

被引:258
作者
Ohki, I
Shimotake, N
Fujita, N
Jee, JG
Ikegami, T
Nakao, M
Shirakawa, M
机构
[1] Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara 6300101, Japan
[2] Yokohama City Univ, Grad Sch Integrated Sci, Kanagawa 2300045, Japan
[3] Kumamoto Univ, Sch Med, Dept Tumor Genet & Biol, Kumamoto 8600811, Japan
关键词
D O I
10.1016/S0092-8674(01)00324-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In vertebrates, the biological consequences of DNA methylation are often mediated by protein factors containing conserved methyl-CpG binding domains (MBDs). Mutations in the MBD protein MeCP2 cause the neurodevelopmental disease Rett syndrome. We report here the solution structure of the MBD of the human methylation-dependent transcriptional regulator MBD1 bound to methylated BRA. DNA binding causes a loop in MBD1 to fold into a major and novel DNA binding interface. Recognition of the methyl groups and CG sequence at the methylation site is due to five highly conserved residues that form a hydrophobic patch. The structure indicates how MBD may access nucleosomal DNA without encountering steric interference from core histones, and provides a basis to interpret mutations linked to Rett syndrome in MeCP2.
引用
收藏
页码:487 / 497
页数:11
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