MeCP2 Protein Stucture

MeCP2 binds methylated CpG dinucleotides

MeCP2 was first discovered as a protein which specifically binds to methylated CpG dinucleotides. This specificity for methylated DNA is achieved via part of the protein called the Methyl-CpG Binding Domain (MBD). The high functional importance of the MBD is emphasised by the finding that many naturally occuring, disease-causing mutations are located within the MBD. Missence mutations, which only change one amino acid leaving the rest of protein unchanged, are tightly clustered in the MBD. From this follows the very important conclusion that the MBD is crucial for MeCP2 function.

Solving the structure of the MBD from MeCP2 helped in understanding how the domain is folded and what the consequences of Rett syndrome mutations within the MBD are. The picture on the left shows the structure of the MBD with Rett Syndrome-causing mutations highlighted. See references 1 and 2.

MeCP2 is a member of a family of proteins all containing a MBD. Other family members are MBD1, MBD2, MBD3 and MBD4. MBD3 is the only family member which does not bind methylated CpG.

The picture on the right shows the structure of the MBD from the MBD1 protein bound to symmetrically methylated CpG. Both methyl groups (marked as bubbles) point to the major DNA groove, where they make contact with amino acids within the MBD.

See reference 3 for further details