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

Cell. 2001 May 18;105(4):487-97. doi: 10.1016/s0092-8674(01)00324-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Binding Sites / physiology
  • Chromosomal Proteins, Non-Histone*
  • DNA Methylation*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Methyl-CpG-Binding Protein 2
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Protein Structure, Tertiary
  • Repressor Proteins* / chemistry
  • Repressor Proteins* / genetics
  • Repressor Proteins* / metabolism
  • Rett Syndrome / genetics
  • Sequence Homology, Amino Acid
  • Transcription Factors

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MBD1 protein, human
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Repressor Proteins
  • Transcription Factors

Associated data

  • PDB/1IG4