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2ch0

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[[Image:2ch0.gif|left|200px]]
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{{STRUCTURE_2ch0| PDB=2ch0 | SCENE= }}
{{STRUCTURE_2ch0| PDB=2ch0 | SCENE= }}
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'''SOLUTION STRUCTURE OF THE HUMAN MAN1 C-TERMINAL DOMAIN (RESIDUES 655-775)'''
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===SOLUTION STRUCTURE OF THE HUMAN MAN1 C-TERMINAL DOMAIN (RESIDUES 655-775)===
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==Overview==
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MAN1 is an integral protein of the inner nuclear membrane that interacts with nuclear lamins and emerin, thus playing a role in nuclear organization. It also binds to chromatin-associated proteins and transcriptional regulators, including the R-Smads, Smad1, Smad2, and Smad3. Mutations in the human gene encoding MAN1 cause sclerosing bone dysplasias, which sometimes have associated skin abnormalities. At the molecular level, these mutations lead to loss of the MAN1-R-Smads interaction, thus perturbing transforming growth factor beta superfamily signaling pathway. As a first step to understanding the physical basis of MAN1 interaction with R-Smads, we here report the structural characterization of the carboxyl-terminal nucleoplasmic region of MAN1, which is responsible for Smad binding. This region exhibits an amino-terminal globular domain adopting a winged helix fold, as found in several Smad-associated sequence-specific DNA binding factors. Consistently, it binds to DNA through the positively charged recognition helix H3 of its winged helix motif. However, it does not show the predicted carboxyl-terminal U2AF homology domain in solution, suggesting that the folding and stability of such a domain in MAN1 depend upon binding to an unidentified partner. Modeling the complex between DNA and the winged helix domain shows that the regions involved in DNA binding are essentially distinct from those reported to be involved in Smad binding. This suggests that MAN1 binds simultaneously to R-Smads and their targeted DNA sequences.
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(as it appears on PubMed at http://www.pubmed.gov), where 16648637 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16648637}}
==About this Structure==
==About this Structure==
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2CH0 is a [[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=2CH0 OCA].
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2CH0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CH0 OCA].
==Reference==
==Reference==
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[[Category: Nuclear protein]]
[[Category: Nuclear protein]]
[[Category: Winged helix motif]]
[[Category: Winged helix motif]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 22:07:12 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 13:28:34 2008''

Revision as of 10:28, 27 July 2008

Image:2ch0.png

Template:STRUCTURE 2ch0

SOLUTION STRUCTURE OF THE HUMAN MAN1 C-TERMINAL DOMAIN (RESIDUES 655-775)

Template:ABSTRACT PUBMED 16648637

About this Structure

2CH0 is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged helix domain., Caputo S, Couprie J, Duband-Goulet I, Konde E, Lin F, Braud S, Gondry M, Gilquin B, Worman HJ, Zinn-Justin S, J Biol Chem. 2006 Jun 30;281(26):18208-15. Epub 2006 Apr 28. PMID:16648637

Page seeded by OCA on Sun Jul 27 13:28:34 2008

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