3c2i

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Revision as of 08:31, 14 May 2008

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Template:STRUCTURE 3c2i

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known disease associated with this structure: Angelman syndrome OMIM:[300005], Encephalopathy, neonatal severe OMIM:[300005], Mental retardation, X-linked, Lubs type OMIM:[300005], Mental retardation, X-linked, syndromic 13 OMIM:[300005], Rett syndrome OMIM:[300005], Rett syndrome, preserved speech variant OMIM:[300005], Autism, susceptibility to, X-linked-3 OMIM:[300005]

About this Structure

3C2I is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

MeCP2 binding to DNA depends upon hydration at methyl-CpG., Ho KL, McNae IW, Schmiedeberg L, Klose RJ, Bird AP, Walkinshaw MD, Mol Cell. 2008 Feb 29;29(4):525-31. PMID:18313390 Page seeded by OCA on Wed May 14 11:31:36 2008