1d9n

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(New page: 200px<br /> <applet load="1d9n" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d9n" /> '''SOLUTION STRUCTURE OF THE METHYL-CPG-BINDIN...)
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'''SOLUTION STRUCTURE OF THE METHYL-CPG-BINDING DOMAIN OF THE METHYLATION-DEPENDENT TRANSCRIPTIONAL REPRESSOR MBD1/PCM1'''<br />
'''SOLUTION STRUCTURE OF THE METHYL-CPG-BINDING DOMAIN OF THE METHYLATION-DEPENDENT TRANSCRIPTIONAL REPRESSOR MBD1/PCM1'''<br />
==Overview==
==Overview==
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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.
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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==
==Disease==
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==About this Structure==
==About this Structure==
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1D9N is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1D9N OCA].
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1D9N is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D9N OCA].
==Reference==
==Reference==
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[[Category: pcm1]]
[[Category: pcm1]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:30:34 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:14:23 2008''

Revision as of 10:14, 21 February 2008


1d9n

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

Contents

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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