8c60: Difference between revisions
New page: '''Unreleased structure''' The entry 8c60 is ON HOLD until Paper Publication Authors: Alfieri, C., Wan, S.M., Muhammad, R. Description: Cryo-EM structure of the human SIN3B full-length... |
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The | ==Cryo-EM structure of the human SIN3B full-length complex at 3.4 Angstrom resolution== | ||
<StructureSection load='8c60' size='340' side='right'caption='[[8c60]], [[Resolution|resolution]] 3.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8c60]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8C60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C60 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=8c60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c60 OCA], [https://pdbe.org/8c60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c60 RCSB], [https://www.ebi.ac.uk/pdbsum/8c60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c60 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/SIN3B_HUMAN SIN3B_HUMAN] SIN3A-related intellectual disability syndrome due to a point mutation. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SIN3B_HUMAN SIN3B_HUMAN] 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. With FOXK1, regulates cell cycle progression probably by repressing cell cycle inhibitor genes expression. As part of the SIN3B complex represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 (PubMed:37137925). SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription (PubMed:21041482).[UniProtKB:Q62141]<ref>PMID:21041482</ref> <ref>PMID:37137925</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Lysine acetylation in histone tails is a key post-translational modification that controls transcription activation. Histone deacetylase complexes remove histone acetylation, thereby repressing transcription and regulating the transcriptional output of each gene. Although these complexes are drug targets and crucial regulators of organismal physiology, their structure and mechanisms of action are largely unclear. Here, we present the structure of a complete human SIN3B histone deacetylase holo-complex with and without a substrate mimic. Remarkably, SIN3B encircles the deacetylase and contacts its allosteric basic patch thereby stimulating catalysis. A SIN3B loop inserts into the catalytic tunnel, rearranges to accommodate the acetyl-lysine moiety, and stabilises the substrate for specific deacetylation, which is guided by a substrate receptor subunit. Our findings provide a model of specificity for a main transcriptional regulator conserved from yeast to human and a resource of protein-protein interactions for future drug designs. | |||
Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex.,Wan MSM, Muhammad R, Koliopoulos MG, Roumeliotis TI, Choudhary JS, Alfieri C Nat Commun. 2023 May 3;14(1):2556. doi: 10.1038/s41467-023-38276-0. PMID:37137925<ref>PMID:37137925</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8c60" style="background-color:#fffaf0;"></div> | ||
[[Category: Alfieri | |||
[[Category: Wan | ==See Also== | ||
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Alfieri C]] | |||
[[Category: Muhammad R]] | |||
[[Category: Wan SM]] | |||
Latest revision as of 09:50, 24 July 2024
Cryo-EM structure of the human SIN3B full-length complex at 3.4 Angstrom resolutionCryo-EM structure of the human SIN3B full-length complex at 3.4 Angstrom resolution
Structural highlights
DiseaseSIN3B_HUMAN SIN3A-related intellectual disability syndrome due to a point mutation. FunctionSIN3B_HUMAN 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. With FOXK1, regulates cell cycle progression probably by repressing cell cycle inhibitor genes expression. As part of the SIN3B complex represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 (PubMed:37137925). SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription (PubMed:21041482).[UniProtKB:Q62141][1] [2] Publication Abstract from PubMedLysine acetylation in histone tails is a key post-translational modification that controls transcription activation. Histone deacetylase complexes remove histone acetylation, thereby repressing transcription and regulating the transcriptional output of each gene. Although these complexes are drug targets and crucial regulators of organismal physiology, their structure and mechanisms of action are largely unclear. Here, we present the structure of a complete human SIN3B histone deacetylase holo-complex with and without a substrate mimic. Remarkably, SIN3B encircles the deacetylase and contacts its allosteric basic patch thereby stimulating catalysis. A SIN3B loop inserts into the catalytic tunnel, rearranges to accommodate the acetyl-lysine moiety, and stabilises the substrate for specific deacetylation, which is guided by a substrate receptor subunit. Our findings provide a model of specificity for a main transcriptional regulator conserved from yeast to human and a resource of protein-protein interactions for future drug designs. Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex.,Wan MSM, Muhammad R, Koliopoulos MG, Roumeliotis TI, Choudhary JS, Alfieri C Nat Commun. 2023 May 3;14(1):2556. doi: 10.1038/s41467-023-38276-0. PMID:37137925[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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