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- PDB-8bpc: Cryo-EM structure of the human SIN3B histone deacetylase core com... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8bpc | ||||||
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Title | Cryo-EM structure of the human SIN3B histone deacetylase core complex with SAHA at 2.8 Angstrom | ||||||
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![]() | GENE REGULATION / HDAC / Chromatin / Cell cycle / transcription | ||||||
Function / homology | ![]() autosome / protein de-2-hydroxyisobutyrylase activity / positive regulation of male mating behavior / negative regulation of peptidyl-lysine acetylation / p75NTR negatively regulates cell cycle via SC1 / epidermal cell differentiation / negative regulation of dendritic spine development / histone decrotonylase activity / behavioral response to ethanol / fungiform papilla formation ...autosome / protein de-2-hydroxyisobutyrylase activity / positive regulation of male mating behavior / negative regulation of peptidyl-lysine acetylation / p75NTR negatively regulates cell cycle via SC1 / epidermal cell differentiation / negative regulation of dendritic spine development / histone decrotonylase activity / behavioral response to ethanol / fungiform papilla formation / positive regulation of interleukin-1 production / negative regulation of MHC class II biosynthetic process / regulation of cell fate specification / negative regulation of stem cell population maintenance / EGR2 and SOX10-mediated initiation of Schwann cell myelination / negative regulation of transcription by competitive promoter binding / regulation of stem cell differentiation / NuRD complex / ESC/E(Z) complex / XY body / cellular response to dopamine / STAT3 nuclear events downstream of ALK signaling / histone deacetylase / cardiac muscle hypertrophy / protein lysine deacetylase activity / positive regulation of signaling receptor activity / response to caffeine / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / embryonic digit morphogenesis / positive regulation of oligodendrocyte differentiation / histone deacetylase activity / Sin3-type complex / positive regulation of stem cell population maintenance / Notch-HLH transcription pathway / Y chromosome / dendrite development / X chromosome / eyelid development in camera-type eye / odontogenesis of dentin-containing tooth / RNA Polymerase I Transcription Initiation / response to amyloid-beta / positive regulation of proteolysis / histone deacetylase complex / hair follicle placode formation / Regulation of MECP2 expression and activity / NF-kappaB binding / positive regulation of collagen biosynthetic process / response to hyperoxia / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / heterochromatin formation / positive regulation of epithelial to mesenchymal transition / cellular response to retinoic acid / MECP2 regulates neuronal receptors and channels / positive regulation of tyrosine phosphorylation of STAT protein / cellular response to transforming growth factor beta stimulus / Regulation of TP53 Activity through Acetylation / heat shock protein binding / response to amphetamine / transcription repressor complex / Regulation of lipid metabolism by PPARalpha / SUMOylation of chromatin organization proteins / phosphatidylinositol binding / negative regulation of cell migration / transcription corepressor binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / response to cocaine / Regulation of PTEN gene transcription / HDACs deacetylate histones / promoter-specific chromatin binding / negative regulation of transforming growth factor beta receptor signaling pathway / circadian regulation of gene expression / response to nicotine / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / protein modification process / NoRC negatively regulates rRNA expression / negative regulation of DNA-binding transcription factor activity / NOTCH1 Intracellular Domain Regulates Transcription / Cytoprotection by HMOX1 / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / histone deacetylase binding / cellular response to hydrogen peroxide / transcription corepressor activity / positive regulation of tumor necrosis factor production / negative regulation of neuron projection development / cellular response to heat / Factors involved in megakaryocyte development and platelet production / histone binding / RNA polymerase II-specific DNA-binding transcription factor binding / Potential therapeutics for SARS / response to lipopolysaccharide / chromosome, telomeric region / chromatin remodeling / response to xenobiotic stimulus / negative regulation of DNA-templated transcription / chromatin binding / positive regulation of cell population proliferation / chromatin / negative regulation of apoptotic process / positive regulation of DNA-templated transcription Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
![]() | Wan, M.S.M. / Muhammad, R. / Koliopolous, M.G. / Alfieri, C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex. Authors: Mandy S M Wan / Reyhan Muhammad / Marios G Koliopoulos / Theodoros I Roumeliotis / Jyoti S Choudhary / Claudio Alfieri / ![]() Abstract: Lysine acetylation in histone tails is a key post-translational modification that controls transcription activation. Histone deacetylase complexes remove histone acetylation, thereby repressing ...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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 236.3 KB | Display | ![]() |
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PDB format | ![]() | 177.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 38.3 KB | Display | |
Data in CIF | ![]() | 56.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 16149MC ![]() 8bpaC ![]() 8bpbC ![]() 8c60C C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 3 types, 3 molecules ABC
#1: Protein | Mass: 129547.133 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 55443.156 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: Q92769, histone deacetylase, Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides |
#3: Protein | Mass: 41257.059 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Non-polymers , 4 types, 50 molecules ![](data/chem/img/SHH.gif)
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![](data/chem/img/CA.gif)
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#4: Chemical | ChemComp-SHH / | ||||
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#5: Chemical | #6: Chemical | #7: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: SIN3B core complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Value: 0.15 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 500 nm |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 28673 / Symmetry type: POINT |