+Open data
-Basic information
Entry | Database: PDB / ID: 8tb9 | ||||||
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Title | PRC2-J119-450 monomer bound to H1-nucleosome | ||||||
Components |
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Keywords | GENE REGULATION / Histone methyl transferase / gene repression / epigenetics / chromatin | ||||||
Function / homology | Function and homology information protein localization to pericentric heterochromatin / hepatocyte homeostasis / regulation of kidney development / cellular response to trichostatin A / regulation of gliogenesis / negative regulation of striated muscle cell differentiation / [histone H3]-lysine27 N-trimethyltransferase / sex chromatin / negative regulation of keratinocyte differentiation / CAF-1 complex ...protein localization to pericentric heterochromatin / hepatocyte homeostasis / regulation of kidney development / cellular response to trichostatin A / regulation of gliogenesis / negative regulation of striated muscle cell differentiation / [histone H3]-lysine27 N-trimethyltransferase / sex chromatin / negative regulation of keratinocyte differentiation / CAF-1 complex / histone H3K27 trimethyltransferase activity / negative regulation of retinoic acid receptor signaling pathway / ubiquitin-modified histone reader activity / response to tetrachloromethane / cerebellar cortex development / random inactivation of X chromosome / primary miRNA binding / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / regulatory ncRNA-mediated heterochromatin formation / histone H3K27 methyltransferase activity / facultative heterochromatin formation / negative regulation of cardiac muscle hypertrophy / negative regulation of cardiac muscle cell proliferation / positive regulation of cell cycle G1/S phase transition / NURF complex / NuRD complex / positive regulation of transcription regulatory region DNA binding / regulation of cell fate specification / negative regulation of DNA recombination / negative regulation of stem cell population maintenance / DNA replication-dependent chromatin assembly / ESC/E(Z) complex / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / chromatin silencing complex / regulation of stem cell differentiation / protein-lysine N-methyltransferase activity / RSC-type complex / negative regulation of stem cell differentiation / Apoptosis induced DNA fragmentation / Transcription of E2F targets under negative control by DREAM complex / pronucleus / cardiac muscle hypertrophy in response to stress / Polo-like kinase mediated events / synaptic transmission, GABAergic / chromosome condensation / positive regulation of dendrite development / histone H3 methyltransferase activity / cardiac muscle cell proliferation / lncRNA binding / histone methyltransferase complex / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / negative regulation of G1/S transition of mitotic cell cycle / spinal cord development / G1 to G0 transition / negative regulation of gene expression, epigenetic / G1/S-Specific Transcription / positive regulation of stem cell population maintenance / ATPase complex / histone methyltransferase activity / Sin3-type complex / negative regulation of transcription elongation by RNA polymerase II / Transcriptional Regulation by E2F6 / oligodendrocyte differentiation / RNA Polymerase I Transcription Initiation / minor groove of adenine-thymine-rich DNA binding / histone deacetylase complex / negative regulation of cell differentiation / G0 and Early G1 / subtelomeric heterochromatin formation / negative regulation of cytokine production involved in inflammatory response / nucleosome binding / RNA polymerase II core promoter sequence-specific DNA binding / ribonucleoprotein complex binding / pericentric heterochromatin / Cyclin E associated events during G1/S transition / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / positive regulation of epithelial to mesenchymal transition / Cyclin A:Cdk2-associated events at S phase entry / spleen development / keratinocyte differentiation / Deposition of new CENPA-containing nucleosomes at the centromere / Regulation of TP53 Activity through Acetylation / protein localization to chromatin / nucleosomal DNA binding / enzyme activator activity / transcription repressor complex / methylated histone binding / SUMOylation of chromatin organization proteins / B cell differentiation / positive regulation of GTPase activity / transcription corepressor binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / liver development / thymus development / negative regulation of cell migration / PRC2 methylates histones and DNA / cellular response to leukemia inhibitory factor / Regulation of PTEN gene transcription / Regulation of endogenous retroelements by KRAB-ZFP proteins / ubiquitin binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Xenopus laevis (African clawed frog) synthetic construct (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | ||||||
Authors | Sauer, P.V. / Cookis, T. / Pavlenko, E. / Nogales, E. / Poepsel, S. | ||||||
Funding support | United States, 1items
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Citation | Journal: Mol Cell / Year: 2024 Title: Activation of automethylated PRC2 by dimerization on chromatin. Authors: Paul V Sauer / Egor Pavlenko / Trinity Cookis / Linda C Zirden / Juliane Renn / Ankush Singhal / Pascal Hunold / Michaela N Hoehne-Wiechmann / Olivia van Ray / Farnusch Kaschani / Markus ...Authors: Paul V Sauer / Egor Pavlenko / Trinity Cookis / Linda C Zirden / Juliane Renn / Ankush Singhal / Pascal Hunold / Michaela N Hoehne-Wiechmann / Olivia van Ray / Farnusch Kaschani / Markus Kaiser / Robert Hänsel-Hertsch / Karissa Y Sanbonmatsu / Eva Nogales / Simon Poepsel / Abstract: Polycomb repressive complex 2 (PRC2) is an epigenetic regulator that trimethylates lysine 27 of histone 3 (H3K27me3) and is essential for embryonic development and cellular differentiation. H3K27me3 ...Polycomb repressive complex 2 (PRC2) is an epigenetic regulator that trimethylates lysine 27 of histone 3 (H3K27me3) and is essential for embryonic development and cellular differentiation. H3K27me3 is associated with transcriptionally repressed chromatin and is established when PRC2 is allosterically activated upon methyl-lysine binding by the regulatory subunit EED. Automethylation of the catalytic subunit enhancer of zeste homolog 2 (EZH2) stimulates its activity by an unknown mechanism. Here, we show that human PRC2 forms a dimer on chromatin in which an inactive, automethylated PRC2 protomer is the allosteric activator of a second PRC2 that is poised to methylate H3 of a substrate nucleosome. Functional assays support our model of allosteric trans-autoactivation via EED, suggesting a previously unknown mechanism mediating context-dependent activation of PRC2. Our work showcases the molecular mechanism of auto-modification-coupled dimerization in the regulation of chromatin-modifying complexes. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8tb9.cif.gz | 727.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8tb9.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8tb9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8tb9_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 8tb9_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 8tb9_validation.xml.gz | 104.2 KB | Display | |
Data in CIF | 8tb9_validation.cif.gz | 156.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tb/8tb9 ftp://data.pdbj.org/pub/pdb/validation_reports/tb/8tb9 | HTTPS FTP |
-Related structure data
Related structure data | 41146MC 8t9gC 8tasC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 9 types, 13 molecules ABEIWJXORUSVY
#1: Protein | Mass: 21209.459 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: H1-0, H1F0, H1FV / Production host: Escherichia coli (E. coli) / References: UniProt: P07305 | ||||||||||
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#2: Protein | Mass: 36251.715 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: JARID2, JMJ / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q92833 | ||||||||||
#4: Protein | Mass: 86174.984 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EZH2, KMT6 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q15910, [histone H3]-lysine27 N-trimethyltransferase | ||||||||||
#7: Protein | Mass: 15435.126 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P84233 #8: Protein | Mass: 11625.634 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P62799 #9: Protein | | Mass: 47709.527 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RBBP4, RBAP48 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q09028 #10: Protein | Mass: 14355.659 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P06897 #11: Protein | Mass: 13655.948 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P02281 #13: Protein | | Mass: 34183.195 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: AEBP2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q6ZN18 |
-Polycomb protein ... , 2 types, 2 molecules DG
#3: Protein | Mass: 72266.359 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SUZ12, CHET9, JJAZ1, KIAA0160 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q15022 |
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#5: Protein | Mass: 50267.691 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EED / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: O75530 |
-DNA chain , 2 types, 2 molecules HT
#6: DNA chain | Mass: 66539.320 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#12: DNA chain | Mass: 65905.852 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-Non-polymers , 1 types, 1 molecules
#14: Chemical | ChemComp-SAH / |
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-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Buffer solution | pH: 7.8 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 55918 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
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