2czy

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'''Solution structure of the NRSF/REST-mSin3B PAH1 complex'''<br />
'''Solution structure of the NRSF/REST-mSin3B PAH1 complex'''<br />
==Overview==
==Overview==
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In non-neuronal cells and neuronal progenitors, many neuron-specific genes, are repressed by a neural restrictive silencer factor (NRSF)/repressor, element 1 silencing transcription factor (REST), which is an essential, transcriptional repressor recruiting the Sin3-HDAC complex. Sin3 contains, four paired amphipathic helix (PAH) domains, PAH1, PAH2, PAH3 and PAH4. A, specific target repressor for Sin3 is likely to bind to one of them, independently. So far, only the tertiary structures of PAH2 domain, complexes, when bound to the Sin3-interacting domains of Mad1 and HBP1, have been determined. Here, we reveal that the N-terminal repressor domain, of NRSF/REST binds to the PAH1 domain of mSin3B, and determine the, structure of the PAH1 domain associated with the NRSF/REST minimal, repressor domain. Compared to the PAH2 structure, PAH1 holds a rather, globular four-helix bundle structure with a semi-ordered C-terminal tail., In contrast to the amphipathic alpha-helix of Mad1 or HBP1 bound to PAH2, the short hydrophobic alpha-helix of NRSF/REST is captured in the cleft of, PAH1. A nuclear hormone receptor corepressor, N-CoR has been found to bind, to the PAH1 domain with a lower affinity than NRSF/REST by using its, C-terminal region, which contains fewer hydrophobic amino acid residues, than the NRSF/REST helix. For strong binding to a repressor, PAH1 seems to, require a short alpha-helix consisting of mostly hydrophobic amino acid, residues within the repressor. Each of the four PAH domains of Sin3 seems, to interact with a characteristic helix of a specific repressor; PAH1, needs a mostly hydrophobic helix and PAH2 needs an amphipathic helix in, each target repressor.
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In non-neuronal cells and neuronal progenitors, many neuron-specific genes are repressed by a neural restrictive silencer factor (NRSF)/repressor element 1 silencing transcription factor (REST), which is an essential transcriptional repressor recruiting the Sin3-HDAC complex. Sin3 contains four paired amphipathic helix (PAH) domains, PAH1, PAH2, PAH3 and PAH4. A specific target repressor for Sin3 is likely to bind to one of them independently. So far, only the tertiary structures of PAH2 domain complexes, when bound to the Sin3-interacting domains of Mad1 and HBP1, have been determined. Here, we reveal that the N-terminal repressor domain of NRSF/REST binds to the PAH1 domain of mSin3B, and determine the structure of the PAH1 domain associated with the NRSF/REST minimal repressor domain. Compared to the PAH2 structure, PAH1 holds a rather globular four-helix bundle structure with a semi-ordered C-terminal tail. In contrast to the amphipathic alpha-helix of Mad1 or HBP1 bound to PAH2, the short hydrophobic alpha-helix of NRSF/REST is captured in the cleft of PAH1. A nuclear hormone receptor corepressor, N-CoR has been found to bind to the PAH1 domain with a lower affinity than NRSF/REST by using its C-terminal region, which contains fewer hydrophobic amino acid residues than the NRSF/REST helix. For strong binding to a repressor, PAH1 seems to require a short alpha-helix consisting of mostly hydrophobic amino acid residues within the repressor. Each of the four PAH domains of Sin3 seems to interact with a characteristic helix of a specific repressor; PAH1 needs a mostly hydrophobic helix and PAH2 needs an amphipathic helix in each target repressor.
==About this Structure==
==About this Structure==
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2CZY is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CZY OCA].
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2CZY is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CZY OCA].
==Reference==
==Reference==
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[[Category: transcriptional repressor]]
[[Category: transcriptional repressor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:24:54 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:54:03 2008''

Revision as of 14:54, 21 February 2008


2czy

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Solution structure of the NRSF/REST-mSin3B PAH1 complex

Overview

In non-neuronal cells and neuronal progenitors, many neuron-specific genes are repressed by a neural restrictive silencer factor (NRSF)/repressor element 1 silencing transcription factor (REST), which is an essential transcriptional repressor recruiting the Sin3-HDAC complex. Sin3 contains four paired amphipathic helix (PAH) domains, PAH1, PAH2, PAH3 and PAH4. A specific target repressor for Sin3 is likely to bind to one of them independently. So far, only the tertiary structures of PAH2 domain complexes, when bound to the Sin3-interacting domains of Mad1 and HBP1, have been determined. Here, we reveal that the N-terminal repressor domain of NRSF/REST binds to the PAH1 domain of mSin3B, and determine the structure of the PAH1 domain associated with the NRSF/REST minimal repressor domain. Compared to the PAH2 structure, PAH1 holds a rather globular four-helix bundle structure with a semi-ordered C-terminal tail. In contrast to the amphipathic alpha-helix of Mad1 or HBP1 bound to PAH2, the short hydrophobic alpha-helix of NRSF/REST is captured in the cleft of PAH1. A nuclear hormone receptor corepressor, N-CoR has been found to bind to the PAH1 domain with a lower affinity than NRSF/REST by using its C-terminal region, which contains fewer hydrophobic amino acid residues than the NRSF/REST helix. For strong binding to a repressor, PAH1 seems to require a short alpha-helix consisting of mostly hydrophobic amino acid residues within the repressor. Each of the four PAH domains of Sin3 seems to interact with a characteristic helix of a specific repressor; PAH1 needs a mostly hydrophobic helix and PAH2 needs an amphipathic helix in each target repressor.

About this Structure

2CZY is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.

Reference

The neural repressor NRSF/REST binds the PAH1 domain of the Sin3 corepressor by using its distinct short hydrophobic helix., Nomura M, Uda-Tochio H, Murai K, Mori N, Nishimura Y, J Mol Biol. 2005 Dec 9;354(4):903-15. Epub 2005 Oct 26. PMID:16288918

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