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- EMDB-16449: Cryo-EM structure of the human SIN3B full-length complex at 3.4 A... -
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Basic information
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Title | Cryo-EM structure of the human SIN3B full-length complex at 3.4 Angstrom resolution | |||||||||
![]() | SIN3B full-length complex | |||||||||
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![]() | Chromatin / Histone deacetylase / HDAC / HYDROLASE | |||||||||
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 / fungiform papilla formation / behavioral response to ethanol ...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 / 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 / ESC/E(Z) complex / regulation of stem cell differentiation / regulation of double-strand break repair / 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 / histone deacetylase activity / positive regulation of oligodendrocyte differentiation / positive regulation of stem cell population maintenance / Y chromosome / NuA4 histone acetyltransferase complex / Notch-HLH transcription pathway / Sin3-type complex / X chromosome / eyelid development in camera-type eye / dendrite development / 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 double-strand break repair via homologous recombination / 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 / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / 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 / heat shock protein binding / response to amphetamine / transcription repressor complex / Regulation of lipid metabolism by PPARalpha / SUMOylation of chromatin organization proteins / phosphatidylinositol binding / transcription corepressor binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / negative regulation of cell migration / 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 / double-strand break repair via homologous recombination / 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 / 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 / nucleosome / negative regulation of neuron projection development / chromatin organization / Factors involved in megakaryocyte development and platelet production / HATs acetylate histones / histone binding / cellular response to heat / regulation of apoptotic process / RNA polymerase II-specific DNA-binding transcription factor binding / Potential therapeutics for SARS / response to lipopolysaccharide Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
![]() | Alfieri C / Wan SM / Muhammad R | |||||||||
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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 26.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.8 KB 19.8 KB | Display Display | ![]() |
Images | ![]() | 80.6 KB | ||
Filedesc metadata | ![]() | 7.4 KB | ||
Others | ![]() ![]() | 23.4 MB 23.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8c60MC ![]() 8bpaC ![]() 8bpbC ![]() 8bpcC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | SIN3B full-length complex | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.134 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: SIN3B full-length complex half map 1
File | emd_16449_half_map_1.map | ||||||||||||
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Annotation | SIN3B full-length complex half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: SIN3B full-length complex half map 2
File | emd_16449_half_map_2.map | ||||||||||||
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Annotation | SIN3B full-length complex half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Human SIN3B complex
Entire | Name: Human SIN3B complex |
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Components |
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-Supramolecule #1: Human SIN3B complex
Supramolecule | Name: Human SIN3B complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 385 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: ![]() |
Molecular weight | Theoretical: 129.547133 KDa |
Recombinant expression | Organism: ![]() |
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: ![]() |
Molecular weight | Theoretical: 55.443156 KDa |
Recombinant expression | Organism: ![]() |
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: ![]() |
Molecular weight | Theoretical: 109.841586 KDa |
Recombinant expression | Organism: ![]() |
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 RIHKKHPPNR RVLQSVKRRS LKVPDAIKSQ YQFPPPLIAP AAIR DGELI CNGIPEESQM HLLNSEHLAT QAEQQEWLCS VVALQCSILK HLSAKQMPSH WDSEQTEKAD IKPVIVTDSS VTTSL QTAD KTPTPSHYPL SCPSGISTQN SLSCSPPHQS PALEDIGCSS CAEKSKKTPC GTANGPVNTE VKANGPHLYS SPTDST DPR RLPGANTPLP GLSHRQGWPR PLTPPAAGGL QNHTVGIIVK TENATGPSSC PQRSLVPVPS LPPSIPSSCA SIENTST LQ RKTVQSQIGP PLTDSRPLGS PPNATRVLTP PQAAGDGILA TTANQRFSSP APSSDGKVSP GTLSIGSALT VPSFPANS T AMVDLTNSLR AFMDVNGEIE INMLDEKLIK FLALQRIHQL FPSRVQPSPG SVGTHQLASG GHHIEVQRKE VQARAVFYP LLGLGGAVNM CYRTLYIGTG ADMDVCLTNY GHCNYVSGKH ACIFYDENTK HYELLNYSEH GTTVDNVLYS CDFSEKTPPT PPSSIVAKV QSVIRRRRHQ KQDEEPSEEA AMMSSQAQGP QRRPCNCKAS SSSLIGGSGA GWEGTALLHH GSYIKLGCLQ F VFSITEFA TKQPKGDASL LQDGVLAEKL SLKPHQGPVL RSNSVP UniProtKB: PHD finger protein 12 |
-Macromolecule #4: Mortality factor 4-like protein 1
Macromolecule | Name: Mortality factor 4-like protein 1 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 41.540484 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MAPKQDPKPK FQEGERVLCF HGPLLYEAKC VKVAIKDKQV KYFIHYSGWN KKSAVRPRRS EKSLKTHEDI VALFPVPEGA PSVHHPLLT SSWDEWVPES RVLKYVDTNL QKQRELQKAN QEQYAEGKMR GAAPGKKTSG LQQKNVEVKT KKNKQKTPGN G DGGSTSET ...String: MAPKQDPKPK FQEGERVLCF HGPLLYEAKC VKVAIKDKQV KYFIHYSGWN KKSAVRPRRS EKSLKTHEDI VALFPVPEGA PSVHHPLLT SSWDEWVPES RVLKYVDTNL QKQRELQKAN QEQYAEGKMR GAAPGKKTSG LQQKNVEVKT KKNKQKTPGN G DGGSTSET PQPPRKKRAR VDPTVENEET FMNRVEVKVK IPEELKPWLV DDWDLITRQK QLFYLPAKKN VDSILEDYAN YK KSRGNTD NKEYAVNEVV AGIKEYFNVM LGTQLLYKFE RPQYAEILAD HPDAPMSQVY GAPHLLRLFV RIGAMLAYTP LDE KSLALL LNYLHDFLKY LAKNSATLFS ASDYEVAPPE YHRKAV UniProtKB: Mortality factor 4-like protein 1 |
-Macromolecule #5: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 5 / Number of copies: 5 / 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 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.6 µm |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 38352 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |