3C2I

The Crystal Structure of Methyl-CpG Binding Domain of Human MeCP2 in Complex with a Methylated DNA Sequence from BDNF

Summary for 3C2I

• Entry DOI: 10.2210/pdb3c2i/pdb
• Descriptor: Methyl-CpG-binding protein 2, DNA (5'-D(*DTP*DCP*DTP*DGP*DGP*DAP*DAP*(5CM)P*DGP*DGP*DAP*DAP*DTP*DTP*DCP*DTP*DTP*DCP*DTP*DA)-3'), DNA (5'-D(*DAP*DTP*DAP*DGP*DAP*DAP*DGP*DAP*DAP*DTP*DTP*DCP*(5CM)P*DGP*DTP*DTP*DCP*DCP*DAP*DG)-3'), ... (4 entities in total)
• Functional Keywords: water mediated recognition, protein-methylated dna complex, asx-st-motif, disease mutation, dna-binding, nucleus, phosphoprotein, repressor, transcription regulator
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P51608
• Total number of polymer chains: 3
• Total formula weight: 23575.42

Authors

Ho, K.L.,McNae, I.W.,Schmiedeberg, L.,Klose, R.J.,Bird, A.P.,Walkinshaw, M.D. (deposition date: 2008-01-25, release date: 2008-05-13, Last modification date: 2024-11-20)

Primary citation

Ho, K.L.,McNae, I.W.,Schmiedeberg, L.,Klose, R.J.,Bird, A.P.,Walkinshaw, M.D.
MeCP2 binding to DNA depends upon hydration at methyl-CpG
Mol.Cell, 29:525-531, 2008

PubMed Abstract: MeCP2 is an essential transcriptional repressor that mediates gene silencing through binding to methylated DNA. Binding specificity has been thought to depend on hydrophobic interactions between cytosine methyl groups and a hydrophobic patch within the methyl-CpG-binding domain (MBD). X-ray analysis of a methylated DNA-MBD cocrystal reveals, however, that the methyl groups make contact with a predominantly hydrophilic surface that includes tightly bound water molecules. This suggests that MeCP2 recognizes hydration of the major groove of methylated DNA rather than cytosine methylation per se. The MeCP2-DNA complex also identifies a unique structural role for T158, the residue most commonly mutated in Rett syndrome.

PubMed: 18313390
DOI: 10.1016/j.molcel.2007.12.028

Experimental method

X-RAY DIFFRACTION (2.5 Å)