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Yorodumi- EMDB-16149: Cryo-EM structure of the human SIN3B histone deacetylase core com... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16149 | |||||||||
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Title | Cryo-EM structure of the human SIN3B histone deacetylase core complex with SAHA at 2.8 Angstrom | |||||||||
Map data | SIN3B-core complex with SAHA | |||||||||
Sample |
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Keywords | HDAC / Chromatin / Cell cycle / transcription / GENE REGULATION | |||||||||
Function / homology | Function and homology information Y chromosome / autosome / X chromosome / 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 ...Y chromosome / autosome / X chromosome / 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 / fungiform papilla formation / behavioral response to ethanol / positive regulation of interleukin-1 production / negative regulation of MHC class II biosynthetic process / NuRD complex / regulation of cell fate specification / EGR2 and SOX10-mediated initiation of Schwann cell myelination / negative regulation of transcription by competitive promoter binding / negative regulation of stem cell population maintenance / eyelid development in camera-type eye / ESC/E(Z) complex / regulation of stem cell differentiation / 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 / SUMOylation of chromatin organization proteins / embryonic digit morphogenesis / histone deacetylase activity / positive regulation of oligodendrocyte differentiation / positive regulation of stem cell population maintenance / Notch-HLH transcription pathway / Sin3-type complex / dendrite development / odontogenesis of dentin-containing tooth / RNA Polymerase I Transcription Initiation / response to amyloid-beta / positive regulation of proteolysis / histone deacetylase complex / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / 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 / positive regulation of epithelial to mesenchymal transition / MECP2 regulates neuronal receptors and channels / cellular response to retinoic acid / positive regulation of tyrosine phosphorylation of STAT protein / cellular response to transforming growth factor beta stimulus / Regulation of TP53 Activity through Acetylation / Regulation of PTEN gene transcription / heat shock protein binding / response to amphetamine / transcription repressor complex / Regulation of lipid metabolism by PPARalpha / phosphatidylinositol binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / transcription corepressor binding / negative regulation of transforming growth factor beta receptor signaling pathway / negative regulation of cell migration / response to cocaine / HDACs deacetylate histones / promoter-specific chromatin binding / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / circadian regulation of gene expression / NoRC negatively regulates rRNA expression / response to nicotine / protein modification process / negative regulation of DNA-binding transcription factor activity / heterochromatin formation / Cytoprotection by HMOX1 / NOTCH1 Intracellular Domain Regulates Transcription / histone deacetylase binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / cellular response to hydrogen peroxide / transcription corepressor activity / positive regulation of tumor necrosis factor production / Factors involved in megakaryocyte development and platelet production / negative regulation of neuron projection development / histone binding / cellular response to heat / chromosome, telomeric region / Potential therapeutics for SARS / RNA polymerase II-specific DNA-binding transcription factor binding / response to lipopolysaccharide / chromatin remodeling / response to xenobiotic stimulus / negative regulation of DNA-templated transcription / chromatin binding / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / chromatin Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
Authors | Wan MSM / Muhammad R / Koliopolous MG / Alfieri C | |||||||||
Funding support | United Kingdom, 1 items
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Citation | Journal: Nat Commun / Year: 2023 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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_16149.map.gz | 3 MB | EMDB map data format | |
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Header (meta data) | emd-16149-v30.xml emd-16149.xml | 19.2 KB 19.2 KB | Display Display | EMDB header |
Images | emd_16149.png | 115.6 KB | ||
Filedesc metadata | emd-16149.cif.gz | 6.9 KB | ||
Others | emd_16149_half_map_1.map.gz emd_16149_half_map_2.map.gz | 29.7 MB 29.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16149 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16149 | HTTPS FTP |
-Validation report
Summary document | emd_16149_validation.pdf.gz | 774.7 KB | Display | EMDB validaton report |
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Full document | emd_16149_full_validation.pdf.gz | 774.3 KB | Display | |
Data in XML | emd_16149_validation.xml.gz | 11 KB | Display | |
Data in CIF | emd_16149_validation.cif.gz | 12.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16149 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16149 | HTTPS FTP |
-Related structure data
Related structure data | 8bpcMC 8bpaC 8bpbC 8c60C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_16149.map.gz / Format: CCP4 / Size: 38.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | SIN3B-core complex with SAHA | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.016 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: SIN3B-core complex with SAHA half map 2
File | emd_16149_half_map_1.map | ||||||||||||
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Annotation | SIN3B-core complex with SAHA half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: SIN3B-core complex with SAHA half map 1
File | emd_16149_half_map_2.map | ||||||||||||
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Annotation | SIN3B-core complex with SAHA half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : SIN3B core complex
Entire | Name: SIN3B core complex |
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Components |
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-Supramolecule #1: SIN3B core complex
Supramolecule | Name: SIN3B core complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 150 KDa |
-Macromolecule #1: Isoform 2 of Paired amphipathic helix protein Sin3b
Macromolecule | Name: Isoform 2 of Paired amphipathic helix protein Sin3b / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 129.547133 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MAHAGGGSGG SGAGGPAGRG LSGARWGRSG SAGHEKLPVH VEDALTYLDQ VKIRFGSDPA TYNGFLEIMK EFKSQSIDTP GVIRRVSQL FHEHPDLIVG FNAFLPLGYR IDIPKNGKLN IQSPLTSQEN SHNHGDGAED FKQQVPYKED KPQVPLESDS V EFNNAISY ...String: MAHAGGGSGG SGAGGPAGRG LSGARWGRSG SAGHEKLPVH VEDALTYLDQ VKIRFGSDPA TYNGFLEIMK EFKSQSIDTP GVIRRVSQL FHEHPDLIVG FNAFLPLGYR IDIPKNGKLN IQSPLTSQEN SHNHGDGAED FKQQVPYKED KPQVPLESDS V EFNNAISY VNKIKTRFLD HPEIYRSFLE ILHTYQKEQL NTRGRPFRGM SEEEVFTEVA NLFRGQEDLL SEFGQFLPEA KR SLFTGNG PCEMHSVQKN EHDKTPEHSR KRSRPSLLRP VSAPAKKKMK LRGTKDLSIA AVGKYGTLQE FSFFDKVRRV LKS QEVYEN FLRCIALFNQ ELVSGSELLQ LVSPFLGKFP ELFAQFKSFL GVKELSFAPP MSDRSGDGIS REIDYASCKR IGSS YRALP KTYQQPKCSG RTAICKEVLN DTWVSFPSWS EDSTFVSSKK TPYEEQLHRC EDERFELDVV LETNLATIRV LESVQ KKLS RMAPEDQEKF RLDDSLGGTS EVIQRRAIYR IYGDKAPEII ESLKKNPVTA VPVVLKRLKA KEEEWREAQQ GFNKIW REQ YEKAYLKSLD HQAVNFKQND TKALRSKSLL NEIESVYDEH QEQHSEGRSA PSSEPHLIFV YEDRQILEDA AALISYY VK RQPAIQKEDQ GTIHQLLHQF VPSLFFSQQL DLGASEESAD EDRDSPQGQT TDPSERKKPA PGPHSSPPEE KGAFGDAP A TEQPPLPPPA PHKPLDDVYS LFFANNNWYF FLRLHQTLCS RLLKIYRQAQ KQLLEYRTEK EREKLLCEGR REKGSDPAM ELRLKQPSEV ELEEYYPAFL DMVRSLLEGS IDPTQYEDTL REMFTIHAYV GFTMDKLVQN IARQLHHLVS DDVCLKVVEL YLNEKKRGA AGGNLSSRCV RAARETSYQW KAERCMADEN CFKVMFLQRK GQVIMTIELL DTEEAQTEDP VEVQHLARYV E QYVGTEGA SSSPTEGFLL KPVFLQRNLK KFRRRWQSEQ ARALRGEARS SWKRLVGVES ACDVDCRFKL STHKMVFIVN SE DYMYRRG TLCRAKQVQP LVLLRHHQHF EEWHSRWLED NVTVEAASLV QDWLMGEEDE DMVPCKTLCE TVHVHGLPVT RYR VQYSRR PASP UniProtKB: Paired amphipathic helix protein Sin3b |
-Macromolecule #2: Histone deacetylase 2
Macromolecule | Name: Histone deacetylase 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: histone deacetylase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 55.443156 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MAYSQGGGKK KVCYYYDGDI GNYYYGQGHP MKPHRIRMTH NLLLNYGLYR KMEIYRPHKA TAEEMTKYHS DEYIKFLRSI RPDNMSEYS KQMQRFNVGE DCPVFDGLFE FCQLSTGGSV AGAVKLNRQQ TDMAVNWAGG LHHAKKSEAS GFCYVNDIVL A ILELLKYH ...String: MAYSQGGGKK KVCYYYDGDI GNYYYGQGHP MKPHRIRMTH NLLLNYGLYR KMEIYRPHKA TAEEMTKYHS DEYIKFLRSI RPDNMSEYS KQMQRFNVGE DCPVFDGLFE FCQLSTGGSV AGAVKLNRQQ TDMAVNWAGG LHHAKKSEAS GFCYVNDIVL A ILELLKYH QRVLYIDIDI HHGDGVEEAF YTTDRVMTVS FHKYGEYFPG TGDLRDIGAG KGKYYAVNFP MRDGIDDESY GQ IFKPIIS KVMEMYQPSA VVLQCGADSL SGDRLGCFNL TVKGHAKCVE VVKTFNLPLL MLGGGGYTIR NVARCWTYET AVA LDCEIP NELPYNDYFE YFGPDFKLHI SPSNMTNQNT PEYMEKIKQR LFENLRMLPH APGVQMQAIP EDAVHEDSGD EDGE DPDKR ISIRASDKRI ACDEEFSDSE DEGEGGRRNV ADHKKGAKKA RIEEDKKETE DKKTDVKEED KSKDNSGEKT DTKGT KSEQ LSNP UniProtKB: Histone deacetylase 2 |
-Macromolecule #3: PHD finger protein 12
Macromolecule | Name: PHD finger protein 12 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 41.257059 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MWEKMETKTI VYDLDTSGGL MEQIQALLAP PKTDEAEKRS RKPEKEPRRS GRATNHDSCD SCKEGGDLLC CDHCPAAFHL QCCNPPLSE EMLPPGEWMC HRCTVRRKKR EQKKELGHVN GLVDKSGKRT TSPSSDTDLL DRSASKTELK AIAHARILER R ASRPGTPT ...String: MWEKMETKTI VYDLDTSGGL MEQIQALLAP PKTDEAEKRS RKPEKEPRRS GRATNHDSCD SCKEGGDLLC CDHCPAAFHL QCCNPPLSE EMLPPGEWMC HRCTVRRKKR EQKKELGHVN GLVDKSGKRT TSPSSDTDLL DRSASKTELK AIAHARILER R ASRPGTPT SSASTETPTS EQNDVDEDII DVDEEPVAAE PDYVQPQLRR PFELLIAAAM ERNPTQFQLP NELTCTTALP GS SKRRRKE ETTGKNVKKT QHELDHNGLV PLPVKVCFTC NRSCRVAPLI QCDYCPLLFH MDCLEPPLTA MPLGRWMCPN HIE HVVLNQ KNMTLSNRCQ VFDRFQDTVS QHVVKVDFLN RIHKKHPP UniProtKB: PHD finger protein 12, PHD finger protein 12 |
-Macromolecule #4: OCTANEDIOIC ACID HYDROXYAMIDE PHENYLAMIDE
Macromolecule | Name: OCTANEDIOIC ACID HYDROXYAMIDE PHENYLAMIDE / type: ligand / ID: 4 / Number of copies: 1 / Formula: SHH |
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Molecular weight | Theoretical: 264.32 Da |
Chemical component information | ChemComp-SHH: |
-Macromolecule #5: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 5 / Number of copies: 3 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #6: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #7: water
Macromolecule | Name: water / type: ligand / ID: 7 / Number of copies: 44 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.5 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 28673 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |