1d9n

From Proteopedia

Revision as of 08:35, 20 March 2008

SOLUTION STRUCTURE OF THE METHYL-CPG-BINDING DOMAIN OF THE METHYLATION-DEPENDENT TRANSCRIPTIONAL REPRESSOR MBD1/PCM1

Overview

CpG methylation in vertebrates is important for gene silencing, alterations in chromatin structure and genomic stability, and differences in the DNA-methylation status are correlated with imprinting phenomena, carcinogenesis and embryonic development. Methylation signals are interpreted by protein factors that contain shared methyl-CpG-binding domains (MBDs). We have determined the solution structure of the MBD of the human methylation-dependent transcriptional repressor MBD1 by multi-dimensional heteronuclear NMR spectroscopy. It folds into an alpha/beta-sandwich structure with characteristic loops. Basic residues conserved in the MBD family are largely confined to one face of this fold and a flexible loop, which together form a large positively charged surface. Site-directed mutagenesis and chemical shift changes upon complexing with a methylated DNA facilitated identification of this surface as the DNA interaction site. In addition to three basic residues, conserved Tyr34 and Asp32 were shown to be important for the DNA binding.

Disease

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

About this Structure

1D9N 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 the methylation-dependent transcriptional repressor MBD1., Ohki I, Shimotake N, Fujita N, Nakao M, Shirakawa M, EMBO J. 1999 Dec 1;18(23):6653-61. PMID:10581239

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