+Open data
-Basic information
Entry | Database: PDB / ID: 7ktp | ||||||
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Title | PRC2:EZH1_B from a dimeric PRC2 bound to a nucleosome | ||||||
Components |
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Keywords | GENE REGULATION/Transferase / Chromatin / methyltransferase / nucleosome-modifying complex / GENE REGULATION / GENE REGULATION-Transferase complex | ||||||
Function / homology | Function and homology information [histone H3]-lysine27 N-trimethyltransferase / sex chromatin / CAF-1 complex / histone H3K27 trimethyltransferase activity / random inactivation of X chromosome / facultative heterochromatin formation / histone H3K27 methyltransferase activity / NURF complex / NuRD complex / regulation of cell fate specification ...[histone H3]-lysine27 N-trimethyltransferase / sex chromatin / CAF-1 complex / histone H3K27 trimethyltransferase activity / random inactivation of X chromosome / facultative heterochromatin formation / histone H3K27 methyltransferase activity / NURF complex / NuRD complex / regulation of cell fate specification / negative regulation of stem cell population maintenance / DNA replication-dependent chromatin assembly / ESC/E(Z) complex / chromatin silencing complex / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / regulation of stem cell differentiation / RSC-type complex / Transcription of E2F targets under negative control by DREAM complex / Polo-like kinase mediated events / G0 and Early G1 / lncRNA binding / Cyclin E associated events during G1/S transition / SUMOylation of chromatin organization proteins / spinal cord development / positive regulation of stem cell population maintenance / G1/S-Specific Transcription / ATPase complex / histone methyltransferase activity / Sin3-type complex / Cyclin A:Cdk2-associated events at S phase entry / oligodendrocyte differentiation / Transcriptional Regulation by E2F6 / RNA Polymerase I Transcription Initiation / negative regulation of cell differentiation / histone deacetylase complex / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / subtelomeric heterochromatin formation / anatomical structure morphogenesis / nucleosome binding / heterochromatin / Deposition of new CENPA-containing nucleosomes at the centromere / enzyme activator activity / Regulation of TP53 Activity through Acetylation / Regulation of PTEN gene transcription / methylated histone binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / transcription corepressor binding / PRC2 methylates histones and DNA / negative regulation of transforming growth factor beta receptor signaling pathway / molecular condensate scaffold activity / negative regulation of cell migration / Defective pyroptosis / HDACs deacetylate histones / promoter-specific chromatin binding / hippocampus development / HCMV Early Events / PKMTs methylate histone lysines / brain development / heterochromatin formation / chromatin DNA binding / Activation of anterior HOX genes in hindbrain development during early embryogenesis / histone deacetylase binding / chromosome / transcription corepressor activity / nucleosome assembly / histone binding / chromosome, telomeric region / DNA replication / Potential therapeutics for SARS / Oxidative Stress Induced Senescence / methylation / cell population proliferation / chromatin remodeling / nuclear body / ribonucleoprotein complex / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of cell population proliferation / negative regulation of DNA-templated transcription / chromatin binding / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / chromatin / regulation of DNA-templated transcription / nucleolus / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.8 Å | ||||||
Authors | Grau, D.J. / Armache, K.J. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2021 Title: Structures of monomeric and dimeric PRC2:EZH1 reveal flexible modules involved in chromatin compaction. Authors: Daniel Grau / Yixiao Zhang / Chul-Hwan Lee / Marco Valencia-Sánchez / Jenny Zhang / Miao Wang / Marlene Holder / Vladimir Svetlov / Dongyan Tan / Evgeny Nudler / Danny Reinberg / Thomas ...Authors: Daniel Grau / Yixiao Zhang / Chul-Hwan Lee / Marco Valencia-Sánchez / Jenny Zhang / Miao Wang / Marlene Holder / Vladimir Svetlov / Dongyan Tan / Evgeny Nudler / Danny Reinberg / Thomas Walz / Karim-Jean Armache / Abstract: Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the ...Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the selective incorporation of one of two paralogs of the catalytic subunit, EZH1 or EZH2. Each of these enzymes has specialized biological functions that may be partially explained by differences in the multivalent interactions they mediate with chromatin. Here, we present two cryo-EM structures of PRC2:EZH1, one as a monomer and a second one as a dimer bound to a nucleosome. When bound to nucleosome substrate, the PRC2:EZH1 dimer undergoes a dramatic conformational change. We demonstrate that mutation of a divergent EZH1/2 loop abrogates the nucleosome-binding and methyltransferase activities of PRC2:EZH1. Finally, we show that PRC2:EZH1 dimers are more effective than monomers at promoting chromatin compaction, and the divergent EZH1/2 loop is essential for this function, thereby tying together the methyltransferase, nucleosome-binding, and chromatin-compaction activities of PRC2:EZH1. We speculate that the conformational flexibility and the ability to dimerize enable PRC2 to act on the varied chromatin substrates it encounters in the cell. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7ktp.cif.gz | 299.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ktp.ent.gz | 227.7 KB | Display | PDB format |
PDBx/mmJSON format | 7ktp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ktp_validation.pdf.gz | 852.9 KB | Display | wwPDB validaton report |
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Full document | 7ktp_full_validation.pdf.gz | 857.2 KB | Display | |
Data in XML | 7ktp_validation.xml.gz | 42.6 KB | Display | |
Data in CIF | 7ktp_validation.cif.gz | 65 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kt/7ktp ftp://data.pdbj.org/pub/pdb/validation_reports/kt/7ktp | HTTPS FTP |
-Related structure data
Related structure data | 23025MC 7ksoC 7ksrC 7ktqC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 85394.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EZH1, KIAA0388 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q92800, [histone H3]-lysine27 N-trimethyltransferase | ||
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#2: 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: Spodoptera frugiperda (fall armyworm) / References: UniProt: O75530 | ||
#3: Protein | Mass: 83181.922 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: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q15022 | ||
#4: 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: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q09028 | ||
#5: Chemical | ChemComp-ZN / Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: PRC2:EZH1_A from a PRC2:EZH1 dimer bound to a nucleosome Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT | |||||||||||||||||||||||||
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Molecular weight | Value: .266 MDa / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||||||||||||
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) | |||||||||||||||||||||||||
Buffer solution | pH: 7.9 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.12 mg/ml / 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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 56.7 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software | Name: cryoSPARC / Category: CTF correction |
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CTF correction | Details: Patch CTF correction / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Particle selection | Num. of particles selected: 3410000 / Details: Template based picking |
3D reconstruction | Resolution: 4.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 26440 / Symmetry type: POINT |