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Yorodumi- PDB-6c23: Cryo-EM structure of PRC2 bound to cofactors AEBP2 and JARID2 in ... -
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-Basic information
Entry | Database: PDB / ID: 6c23 | ||||||||||||
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Title | Cryo-EM structure of PRC2 bound to cofactors AEBP2 and JARID2 in the Compact Active State | ||||||||||||
Components |
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Keywords | GENE REGULATION / polycomb repressive complex / AEBP2 / JARID2 / histone modification | ||||||||||||
Function / homology | Function and homology information protein localization to pericentric heterochromatin / regulation of kidney development / hepatocyte homeostasis / cellular response to trichostatin A / regulation of gliogenesis / [histone H3]-lysine27 N-trimethyltransferase / negative regulation of striated muscle cell differentiation / sex chromatin / CAF-1 complex / negative regulation of keratinocyte differentiation ...protein localization to pericentric heterochromatin / regulation of kidney development / hepatocyte homeostasis / cellular response to trichostatin A / regulation of gliogenesis / [histone H3]-lysine27 N-trimethyltransferase / negative regulation of striated muscle cell differentiation / sex chromatin / CAF-1 complex / negative regulation of keratinocyte differentiation / histone H3K27 trimethyltransferase activity / negative regulation of retinoic acid receptor signaling pathway / random inactivation of X chromosome / primary miRNA binding / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / response to tetrachloromethane / ubiquitin modification-dependent histone binding / cerebellar cortex development / histone H3K27 methyltransferase activity / negative regulation of cardiac muscle hypertrophy / positive regulation of cell cycle G1/S phase transition / negative regulation of cardiac muscle cell proliferation / facultative heterochromatin formation / NURF complex / NuRD complex / regulation of cell fate specification / DNA replication-dependent chromatin assembly / negative regulation of stem cell population maintenance / RSC-type complex / chromatin silencing complex / : / Transcription of E2F targets under negative control by DREAM complex / ESC/E(Z) complex / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / regulation of stem cell differentiation / protein-lysine N-methyltransferase activity / negative regulation of stem cell differentiation / dosage compensation by inactivation of X chromosome / lncRNA binding / pronucleus / cardiac muscle hypertrophy in response to stress / Polo-like kinase mediated events / synaptic transmission, GABAergic / positive regulation of dendrite development / histone H3 methyltransferase activity / cardiac muscle cell proliferation / histone methyltransferase complex / negative regulation of gene expression, epigenetic / Sin3-type complex / : / negative regulation of G1/S transition of mitotic cell cycle / G1 to G0 transition / ATPase complex / spinal cord development / G1/S-Specific Transcription / positive regulation of stem cell population maintenance / histone methyltransferase activity / negative regulation of transcription elongation by RNA polymerase II / Transcriptional Regulation by E2F6 / oligodendrocyte differentiation / RNA Polymerase I Transcription Initiation / negative regulation of cell differentiation / subtelomeric heterochromatin formation / histone deacetylase complex / G0 and Early G1 / enzyme activator activity / negative regulation of cytokine production involved in inflammatory response / positive regulation of epithelial to mesenchymal transition / RNA polymerase II core promoter sequence-specific DNA binding / protein localization to chromatin / ribonucleoprotein complex binding / pericentric heterochromatin / heterochromatin formation / Cyclin E associated events during G1/S transition / Cyclin A:Cdk2-associated events at S phase entry / Deposition of new CENPA-containing nucleosomes at the centromere / keratinocyte differentiation / spleen development / methylated histone binding / Regulation of TP53 Activity through Acetylation / SUMOylation of chromatin organization proteins / B cell differentiation / negative regulation of cell migration / transcription corepressor binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / thymus development / liver development / cellular response to leukemia inhibitory factor / PRC2 methylates histones and DNA / Regulation of PTEN gene transcription / ubiquitin binding / central nervous system development / Defective pyroptosis / liver regeneration / HDACs deacetylate histones / promoter-specific chromatin binding / stem cell differentiation / hippocampus development / transcription coregulator activity / G1/S transition of mitotic cell cycle Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
Authors | Kasinath, V. / Faini, M. / Poepsel, S. / Reif, D. / Feng, A. / Stjepanovic, G. / Aebersold, R. / Nogales, E. | ||||||||||||
Funding support | United States, European Union, 3items
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Citation | Journal: Science / Year: 2018 Title: Structures of human PRC2 with its cofactors AEBP2 and JARID2. Authors: Vignesh Kasinath / Marco Faini / Simon Poepsel / Dvir Reif / Xinyu Ashlee Feng / Goran Stjepanovic / Ruedi Aebersold / Eva Nogales / Abstract: Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron ...Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron microscopy structures of human PRC2 in a basal state and two distinct active states while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex. Our analysis defines the complete architecture of a functionally relevant PRC2 and provides a structural framework to understand its regulation by cofactors, histone tails, and RNA. | ||||||||||||
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 | 6c23.cif.gz | 424.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6c23.ent.gz | 304.7 KB | Display | PDB format |
PDBx/mmJSON format | 6c23.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c2/6c23 ftp://data.pdbj.org/pub/pdb/validation_reports/c2/6c23 | HTTPS FTP |
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-Related structure data
Related structure data | 7334MC 7335C 7337C 6c24C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Polycomb protein ... , 2 types, 4 molecules AMQL
#1: Protein | Mass: 83181.922 Da / Num. of mol.: 3 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 #4: 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 |
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-Protein , 6 types, 7 molecules EKCNPZB
#2: Protein | Mass: 37936.629 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 | ||||||||
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#3: Protein | Mass: 85492.297 Da / Num. of mol.: 2 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-lysine N-methyltransferase #5: 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 #7: Protein | | Mass: 33012.668 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 #8: Protein | | Mass: 11507.176 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Trichoplusia ni (cabbage looper) #9: Protein | | Mass: 37706.449 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 |
-Protein/peptide , 1 types, 1 molecules O
#6: Protein/peptide | Mass: 735.874 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Trichoplusia ni (cabbage looper) |
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-Details
Sequence details | authors have indicated that the macromolecule name is corresponding to chain Z is SUZ12. The ...authors have indicated that the macromolecule name is corresponding to chain Z is SUZ12. The expected sequence for this portion is: SUZ12 aa 150 - 356 SHSLSAHLQL |
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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 |
-Sample preparation
Component | Name: Ternary complex of PRC2 with cofactors AEBP2 and JARID2 Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.3 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
Buffer solution | pH: 7.9 |
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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 60 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Phase plate: Volta Phase Plate |
-Processing
Software | Name: REFMAC / Version: 5.8.0088 / Classification: refinement | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING ONLY | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 145592 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 3.9→147.84 Å / Cor.coef. Fo:Fc: 0.825 / SU B: 38.798 / SU ML: 0.506 / ESU R: 1.593 Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 120.59 Å2
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Refinement step | Cycle: 1 / Total: 13478 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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