title: Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA.
abstract: 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 DNA. 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.
authors.affiliation: Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, 630-0101, Nara, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Ohki
authors.forename: N
authors.initials: N
authors.lastname: Shimotake
authors.forename: N
authors.initials: N
authors.lastname: Fujita
authors.forename: J
authors.initials: J
authors.lastname: Jee
authors.forename: T
authors.initials: T
authors.lastname: Ikegami
authors.forename: M
authors.initials: M
authors.lastname: Nakao
authors.forename: M
authors.initials: M
authors.lastname: Shirakawa
mesh_terms: D000107:Acetylation; D001665:Binding Sites / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015518:Rett Syndrome / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C066141:MBD1 protein, human; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins; D014157:Transcription Factors