Methyl CpG binding protein

From Proteopedia

(Redirected from MeCP2)

1 Function
2 Disease
3 Relevance
4 Structural highlights
5 3D structures of methyl CpG binding protein

Function

Methyl CpG binding proteins are called MBD1 to MBD4 and contain a methyl-CpG binding domain (MBD) which binds to methylated DNA^[1].
• MBD1 is a transcription regulator. It reverts methylated cytosine bases to cytosine.
• MBD2 is part of the MeCP1 complex which contains also NuRD. MBD2 recruits histone deacetylases and DNA methyltransferases. MBD2 functions as a scaffold protein promoting repression.
• MBD3 binds to hydroxymethylated DNA.
• MBD4 has a G:T mispair-specific activity.
• Methyl CpG binding protein 2 (MeCP2) is present in mature nerve cells and is involved in turning off several genes. For more details see Methyl CpG Binding Protein 2 and Rett Syndrome Protein.

Disease

Mutations in MBD2 are involved in Rett syndrome^[2].

Relevance

MBD1 has a role in lung, prostate, pancreatic, colorectal cancers and promyelocytic leukemia. MBD2 has a role in lung, prostate, renal, colorectal cancers. MBD3 has a role in lung, prostate, ovarian cancers and promyelocytic leukemia. MBD4 has a role in gastric, liver and colorectal cancers.

Structural highlights

Thymine from the mismatched G:T pair flips out from the DNA strand and interchelates with MBD4 residues Lys and Leu^[3].

3D structures of methyl CpG binding protein

Methyl CpG binding protein 3D structures

Structure of mouse MBD4 glycosylate domain complex with DNA containing mismatch, ethylene glycol and Ni+2 ion (green) (PDB code 4evv).

Drag the structure with the mouse to rotate

References

↑ Wade PA. Methyl CpG-binding proteins and transcriptional repression. Bioessays. 2001 Dec;23(12):1131-7. PMID:11746232 doi:http://dx.doi.org/10.1002/bies.10008
↑ Van den Veyver IB, Zoghbi HY. Mutations in the gene encoding methyl-CpG-binding protein 2 cause Rett syndrome. Brain Dev. 2001 Dec;23 Suppl 1:S147-51. PMID:11738862
↑ Hashimoto H, Zhang X, Cheng X. Excision of thymine and 5-hydroxymethyluracil by the MBD4 DNA glycosylase domain: structural basis and implications for active DNA demethylation. Nucleic Acids Res. 2012 Jun 27. PMID:22740654 doi:10.1093/nar/gks628