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| | ==Solution structure of the NRSF/REST-mSin3B PAH1 complex== | | ==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]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <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> | + | <table><tr><td colspan='2'>[[2czy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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> | | <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> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Mori, N]] | + | [[Category: Mori N]] |
| - | [[Category: Murai, K]] | + | [[Category: Murai K]] |
| - | [[Category: Nishimura, Y]] | + | [[Category: Nishimura Y]] |
| - | [[Category: Nomura, M]] | + | [[Category: Nomura M]] |
| - | [[Category: Uda-Tochio, H]] | + | [[Category: Uda-Tochio H]] |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Nrsf]]
| + | |
| - | [[Category: Pah1]]
| + | |
| - | [[Category: Sin3]]
| + | |
| - | [[Category: Transcriptional repressor]]
| + | |
| Structural highlights
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]
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[3]
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
- ↑ 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
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