1ig4

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1ig4

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Solution Structure of the Methyl-CpG-Binding Domain of Human MBD1 in Complex with Methylated DNA

Contents

Overview

In vertebrates, the biological consequences of DNA methylation are often, mediated by protein factors containing conserved methyl-CpG binding, domains (MBDs). Mutations in the MBD protein MeCP2 cause the, neurodevelopmental disease Rett syndrome. We report here the solution, structure of the MBD of the human methylation-dependent transcriptional, regulator MBD1 bound to methylated DNA. DNA binding causes a loop in MBD1, to fold into a major and novel DNA binding interface. Recognition of the, methyl groups and CG sequence at the methylation site is due to five, highly conserved residues that form a hydrophobic patch. The structure, indicates how MBD may access nucleosomal DNA without encountering steric, interference from core histones, and provides a basis to interpret, mutations linked to Rett syndrome in MeCP2.

Disease

Known disease associated with this structure: Thyroid carcinoma, papillary OMIM:[600299]

About this Structure

1IG4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA., Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, Shirakawa M, Cell. 2001 May 18;105(4):487-97. PMID:11371345

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