Summary information and primary citation

3c2i; SNAP-derived features in text and JSON formats; DNAproDB
transcription regulator
X-ray (2.5 Å)
The crystal structure of methyl-cpg binding domain of human mecp2 in complex with a methylated DNA sequence from bdnf
Ho KL, McNae IW, Schmiedeberg L, Klose RJ, Bird AP, Walkinshaw MD (2008): "MeCP2 binding to DNA depends upon hydration at methyl-CpG." Mol.Cell, 29, 525-531. doi: 10.1016/j.molcel.2007.12.028.
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.

Cartoon-block schematics in six views (download the tarball)

PyMOL session file Download PDB file View in 3Dmol.js

List of 2 5mC-amino acid contacts

No. 1 B.5CM8: stacking-with-A.ARG111 is-WC-paired is-in-duplex [+]:AcG/cGT
No. 2 C.5CM33: stacking-with-A.ARG133 is-WC-paired is-in-duplex [-]:cGG/CcG