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Open data
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Basic information
Entry | Database: PDB / ID: 6wkr | ||||||
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Title | PRC2-AEBP2-JARID2 bound to H2AK119ub1 nucleosome | ||||||
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![]() | GENE REGULATION/DNA / chromatin / nucleosome / transcription / cryo-EM / ubiquitination / gene regulation-DNA complex / heterochromatin / DNA binding | ||||||
Function / homology | ![]() 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 / ubiquitin-modified histone reader activity / regulatory ncRNA-mediated heterochromatin formation / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / response to tetrachloromethane / cerebellar cortex development / facultative heterochromatin formation / 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 / 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 / protein-lysine N-methyltransferase activity / negative regulation of stem cell differentiation / RSC-type complex / 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 / G0 and Early G1 / positive regulation of dendrite development / histone H3 methyltransferase activity / lncRNA binding / cardiac muscle cell proliferation / Cyclin E associated events during G1/S transition / SUMOylation of chromatin organization proteins / histone methyltransferase complex / negative regulation of G1/S transition of mitotic cell cycle / G1 to G0 transition / negative regulation of gene expression, epigenetic / 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 / negative regulation of transcription elongation by RNA polymerase II / 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 / negative regulation of cytokine production involved in inflammatory response / RNA polymerase II core promoter sequence-specific DNA binding / pericentric heterochromatin / ribonucleoprotein complex binding / positive regulation of epithelial to mesenchymal transition / Deposition of new CENPA-containing nucleosomes at the centromere / keratinocyte differentiation / transcription coregulator activity / Maturation of protein E / Maturation of protein E / spleen development / ER Quality Control Compartment (ERQC) / protein localization to chromatin / Myoclonic epilepsy of Lafora / enzyme activator activity / FLT3 signaling by CBL mutants / Regulation of TP53 Activity through Acetylation / Regulation of PTEN gene transcription / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
![]() | Kasinath, V. / Nogales, E. / Beck, C. / Sauer, P. / Poepsel, S. / Kosmatka, J. / Faini, M. / Toso, D. / Aebersold, R. | ||||||
Funding support | ![]()
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![]() | ![]() Title: JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications. Authors: Vignesh Kasinath / Curtis Beck / Paul Sauer / Simon Poepsel / Jennifer Kosmatka / Marco Faini / Daniel Toso / Ruedi Aebersold / Eva Nogales / ![]() ![]() ![]() Abstract: Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) cooperate to determine cell identity by epigenetic gene expression regulation. However, the mechanism of PRC2 recruitment by means of recognition ...Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) cooperate to determine cell identity by epigenetic gene expression regulation. However, the mechanism of PRC2 recruitment by means of recognition of PRC1-mediated H2AK119ub1 remains poorly understood. Our PRC2 cryo-electron microscopy structure with cofactors JARID2 and AEBP2 bound to a H2AK119ub1-containing nucleosome reveals a bridge helix in EZH2 that connects the SET domain, H3 tail, and nucleosomal DNA. JARID2 and AEBP2 each interact with one ubiquitin and the H2A-H2B surface. JARID2 stimulates PRC2 through interactions with both the polycomb protein EED and the H2AK119-ubiquitin, whereas AEBP2 has an additional scaffolding role. The presence of these cofactors partially overcomes the inhibitory effect that H3K4me3 and H3K36me3 exert on core PRC2 (in the absence of cofactors). Our results support a key role for JARID2 and AEBP2 in the cross-talk between histone modifications and PRC2 activity. | ||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 719.4 KB | Display | ![]() |
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PDB format | ![]() | 559.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 21707MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 9 types, 15 molecules TFNCBEPIOJQKRMS
#1: Protein | Mass: 8622.922 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | | Mass: 47709.527 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #5: Protein | | Mass: 85492.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: Q15910, [histone H3]-lysine27 N-trimethyltransferase #6: Protein | Mass: 49306.074 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #7: Protein | | Mass: 33012.668 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #9: Protein | Mass: 15421.101 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #10: Protein | Mass: 11394.426 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #11: Protein | Mass: 14067.398 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #12: Protein | Mass: 13979.291 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Polycomb protein ... , 2 types, 2 molecules AL
#2: Protein | Mass: 83181.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#3: Protein | Mass: 50267.691 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-DNA chain , 1 types, 1 molecules H
#8: DNA chain | Mass: 98186.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
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-Non-polymers , 3 types, 3 molecules ![](data/chem/img/MG.gif)
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#13: Chemical | ChemComp-MG / |
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#14: Chemical | ChemComp-SAH / |
#15: Chemical | ChemComp-ZN / |
-Details
Has ligand of interest | Y |
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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 |
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Sample preparation
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Molecular weight | Value: 0.5 MDa / Experimental value: NO | ||||||||||||||||||||||||
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Source (recombinant) |
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Buffer solution | pH: 7.9 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R2/2 | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 278 K |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 168601 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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