2czy

From Proteopedia

(Difference between revisions)

Revision as of 11:53, 3 February 2021

Solution structure of the NRSF/REST-mSin3B PAH1 complex

Structural highlights

2czy is a 2 chain structure with sequence from Lk3 transgenic mice. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Sin3B (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SIN3B_MOUSE] Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription.^[1] ^[2] [REST_HUMAN] Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. Restricts the expression of neuronal genes by associating with two distinct corepressors, mSin3 and CoREST, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier.^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ayer DE, Lawrence QA, Eisenman RN. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell. 1995 Mar 10;80(5):767-76. PMID:7889570
↑ Yang Q, Kong Y, Rothermel B, Garry DJ, Bassel-Duby R, Williams RS. The winged-helix/forkhead protein myocyte nuclear factor beta (MNF-beta) forms a co-repressor complex with mammalian sin3B. Biochem J. 2000 Jan 15;345 Pt 2:335-43. PMID:10620510
↑ Chong JA, Tapia-Ramirez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC, Altshuller YM, Frohman MA, Kraner SD, Mandel G. REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell. 1995 Mar 24;80(6):949-57. PMID:7697725
↑ Schoenherr CJ, Anderson DJ. The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science. 1995 Mar 3;267(5202):1360-3. PMID:7871435
↑ Scholl T, Stevens MB, Mahanta S, Strominger JL. A zinc finger protein that represses transcription of the human MHC class II gene, DPA. J Immunol. 1996 Feb 15;156(4):1448-57. PMID:8568247
↑ Lunyak VV, Burgess R, Prefontaine GG, Nelson C, Sze SH, Chenoweth J, Schwartz P, Pevzner PA, Glass C, Mandel G, Rosenfeld MG. Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science. 2002 Nov 29;298(5599):1747-52. Epub 2002 Oct 24. PMID:12399542 doi:10.1126/science.1076469
↑ Nomura M, Uda-Tochio H, Murai K, Mori N, Nishimura Y. The neural repressor NRSF/REST binds the PAH1 domain of the Sin3 corepressor by using its distinct short hydrophobic helix. J Mol Biol. 2005 Dec 9;354(4):903-15. Epub 2005 Oct 26. PMID:16288918 doi:http://dx.doi.org/10.1016/j.jmb.2005.10.008

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2czy"

@@ Line 1: / Line 1: @@
 ==Solution structure of the NRSF/REST-mSin3B PAH1 complex==
-<StructureSection load='2czy' size='340' side='right' caption='[[2czy]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2czy' size='340' side='right'caption='[[2czy]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2czy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CZY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CZY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2czy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CZY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CZY FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sin3B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sin3B ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2czy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2czy OCA], [http://pdbe.org/2czy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2czy RCSB], [http://www.ebi.ac.uk/pdbsum/2czy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2czy ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2czy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2czy OCA], [https://pdbe.org/2czy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2czy RCSB], [https://www.ebi.ac.uk/pdbsum/2czy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2czy ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/SIN3B_MOUSE SIN3B_MOUSE]] Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription.<ref>PMID:7889570</ref> <ref>PMID:10620510</ref>  [[http://www.uniprot.org/uniprot/REST_HUMAN REST_HUMAN]] Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. Restricts the expression of neuronal genes by associating with two distinct corepressors, mSin3 and CoREST, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier.<ref>PMID:7697725</ref> <ref>PMID:7871435</ref> <ref>PMID:8568247</ref> <ref>PMID:12399542</ref>
+[[https://www.uniprot.org/uniprot/SIN3B_MOUSE SIN3B_MOUSE]] Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription.<ref>PMID:7889570</ref> <ref>PMID:10620510</ref>  [[https://www.uniprot.org/uniprot/REST_HUMAN REST_HUMAN]] Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. Restricts the expression of neuronal genes by associating with two distinct corepressors, mSin3 and CoREST, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier.<ref>PMID:7697725</ref> <ref>PMID:7871435</ref> <ref>PMID:8568247</ref> <ref>PMID:12399542</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 32: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Mori, N]]

2czy

From Proteopedia

Revision as of 11:53, 3 February 2021

Solution structure of the NRSF/REST-mSin3B PAH1 complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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