Cover:A homology model of the methyl-binding domain (MBD) of MECP2 interacting with a symmetrically methylated CpG
within a DNA duplex. To construct this model, the NMR solution structure of the MBD of MeCP2 [Wakefield et al. (1999) J. Mol. Biol., 291, 1055-1065] was superimposed on the solution structure of the MBD of MBD1 bound to a symmetrically methylated
DNA sequence [Ohki et al. (2001) Cell, 105, 487-497] using the Insight computational package. The methyl groups of the
5-methylcytosine residues are in yellow. The white ribbon represents the secondary structure of the backbone of the protein, and
the remainder of the protein is the white mesh. This model illustrates the proximity of the methyl groups on the complementary
strands within the major groove of a B-form DNA helix as well as points of hydrophobic interactions between the methyl groups
and the MBD. Oxidative damage to major contact points within the methyl-CpG dinucleotide significantly inhibits MBD binding.
For further details see the paper by Valinluck et al. in this issue [Nucleic Acids Res. (2004) 32, 4100-4108].
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