1ozj

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(New page: 200px<br /> <applet load="1ozj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ozj, resolution 2.4&Aring;" /> '''Crystal structure of...)
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[[Image:1ozj.gif|left|200px]]<br /><applet load="1ozj" size="350" color="white" frame="true" align="right" spinBox="true"
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<applet load="1ozj" size="450" color="white" frame="true" align="right" spinBox="true"
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caption="1ozj, resolution 2.4&Aring;" />
caption="1ozj, resolution 2.4&Aring;" />
'''Crystal structure of Smad3-MH1 bound to DNA at 2.4 A resolution'''<br />
'''Crystal structure of Smad3-MH1 bound to DNA at 2.4 A resolution'''<br />
==Overview==
==Overview==
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The Smad family of proteins mediates transforming growth factor-beta, signaling from cell membrane to the nucleus. In the nucleus, Smads serve, as transcription factors by directly binding to specific DNA sequences and, regulating the expression of ligand-response genes. A previous structural, analysis, at 2.8-A resolution, revealed a novel DNA-binding mode for the, Smad MH1 domain but did not allow accurate assignment of the fines, features of protein-DNA interactions. The crystal structure of a Smad3 MH1, domain bound to a palindromic DNA sequence, determined at 2.4-A, resolution, reveals a surprisingly important role for water molecules. The, asymmetric placement of the DNA-binding motif (a conserved 11-residue, beta-hairpin) in the major groove of DNA is buttressed by seven well, ordered water molecules. These water molecules make specific hydrogen, bonds to the DNA bases, the DNA phosphate backbones, and several critical, Smad3 residues. In addition, the MH1 domain is found to contain a bound, zinc atom using four invariant residues among Smad proteins, three, cysteines and one histidine. Removal of the zinc atom results in, compromised DNA binding activity. These results define the Smad MH1 domain, as a zinc-coordinating module that exhibits unique DNA binding properties.
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The Smad family of proteins mediates transforming growth factor-beta signaling from cell membrane to the nucleus. In the nucleus, Smads serve as transcription factors by directly binding to specific DNA sequences and regulating the expression of ligand-response genes. A previous structural analysis, at 2.8-A resolution, revealed a novel DNA-binding mode for the Smad MH1 domain but did not allow accurate assignment of the fines features of protein-DNA interactions. The crystal structure of a Smad3 MH1 domain bound to a palindromic DNA sequence, determined at 2.4-A resolution, reveals a surprisingly important role for water molecules. The asymmetric placement of the DNA-binding motif (a conserved 11-residue beta-hairpin) in the major groove of DNA is buttressed by seven well ordered water molecules. These water molecules make specific hydrogen bonds to the DNA bases, the DNA phosphate backbones, and several critical Smad3 residues. In addition, the MH1 domain is found to contain a bound zinc atom using four invariant residues among Smad proteins, three cysteines and one histidine. Removal of the zinc atom results in compromised DNA binding activity. These results define the Smad MH1 domain as a zinc-coordinating module that exhibits unique DNA binding properties.
==About this Structure==
==About this Structure==
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1OZJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1OZJ OCA].
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1OZJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OZJ OCA].
==Reference==
==Reference==
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[[Category: Chai, J.]]
[[Category: Chai, J.]]
[[Category: Massague, J.]]
[[Category: Massague, J.]]
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[[Category: Pavletich, N.P.]]
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[[Category: Pavletich, N P.]]
[[Category: Shi, Y.]]
[[Category: Shi, Y.]]
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[[Category: Wu, J.W.]]
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[[Category: Wu, J W.]]
[[Category: Yan, N.]]
[[Category: Yan, N.]]
[[Category: ZN]]
[[Category: ZN]]
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[[Category: zinc-binding module]]
[[Category: zinc-binding module]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:38:31 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:23:24 2008''

Revision as of 12:23, 21 February 2008


1ozj, resolution 2.4Å

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Crystal structure of Smad3-MH1 bound to DNA at 2.4 A resolution

Overview

The Smad family of proteins mediates transforming growth factor-beta signaling from cell membrane to the nucleus. In the nucleus, Smads serve as transcription factors by directly binding to specific DNA sequences and regulating the expression of ligand-response genes. A previous structural analysis, at 2.8-A resolution, revealed a novel DNA-binding mode for the Smad MH1 domain but did not allow accurate assignment of the fines features of protein-DNA interactions. The crystal structure of a Smad3 MH1 domain bound to a palindromic DNA sequence, determined at 2.4-A resolution, reveals a surprisingly important role for water molecules. The asymmetric placement of the DNA-binding motif (a conserved 11-residue beta-hairpin) in the major groove of DNA is buttressed by seven well ordered water molecules. These water molecules make specific hydrogen bonds to the DNA bases, the DNA phosphate backbones, and several critical Smad3 residues. In addition, the MH1 domain is found to contain a bound zinc atom using four invariant residues among Smad proteins, three cysteines and one histidine. Removal of the zinc atom results in compromised DNA binding activity. These results define the Smad MH1 domain as a zinc-coordinating module that exhibits unique DNA binding properties.

About this Structure

1OZJ is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding., Chai J, Wu JW, Yan N, Massague J, Pavletich NP, Shi Y, J Biol Chem. 2003 May 30;278(22):20327-31. Epub 2003 Apr 9. PMID:12686552

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