+Open data
-Basic information
Entry | Database: PDB / ID: 6pwx | |||||||||
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Title | Cryo-EM structure of RbBP5 bound to the nucleosome | |||||||||
Components |
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Keywords | Histone Binding/DNA Binding/DNA / Mixed-Lineage Leukemia / MLL1 / nucleosome / histone H3 Lys4 methyltransferase / RbBP5 / WDR5 / ASH2L / DPY30 / Histone Binding-DNA Binding-DNA complex | |||||||||
Function / homology | Function and homology information MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes / MLL1 complex / transcription initiation-coupled chromatin remodeling / Deactivation of the beta-catenin transactivating complex / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function ...MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes / MLL1 complex / transcription initiation-coupled chromatin remodeling / Deactivation of the beta-catenin transactivating complex / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / PKMTs methylate histone lysines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / response to estrogen / structural constituent of chromatin / nucleosome / nucleosome assembly / Neddylation / histone binding / transcription cis-regulatory region binding / protein heterodimerization activity / DNA damage response / nucleolus / DNA binding / nucleoplasm / nucleus 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: 4.2 Å | |||||||||
Authors | Park, S.H. / Ayoub, A. / Lee, Y.T. / Xu, J. / Zhang, W. / Zhang, B. / Zhang, Y. / Cianfrocco, M.A. / Su, M. / Dou, Y. / Cho, U. | |||||||||
Funding support | United States, Korea, Republic Of, 2items
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Citation | Journal: Nat Commun / Year: 2019 Title: Cryo-EM structure of the human MLL1 core complex bound to the nucleosome. Authors: Sang Ho Park / Alex Ayoub / Young-Tae Lee / Jing Xu / Hanseong Kim / Wei Zheng / Biao Zhang / Liang Sha / Sojin An / Yang Zhang / Michael A Cianfrocco / Min Su / Yali Dou / Uhn-Soo Cho / Abstract: Mixed lineage leukemia (MLL) family histone methyltransferases are enzymes that deposit histone H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive ...Mixed lineage leukemia (MLL) family histone methyltransferases are enzymes that deposit histone H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural and biochemical studies, the molecular mechanisms whereby the MLL complexes recognize histone H3K4 within nucleosome core particles (NCPs) remain unclear. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the NCP-bound human MLL1 core complex. We show that the MLL1 core complex anchors to the NCP via the conserved RbBP5 and ASH2L, which interact extensively with nucleosomal DNA and the surface close to the N-terminal tail of histone H4. Concurrent interactions of RbBP5 and ASH2L with the NCP uniquely align the catalytic MLL1 domain at the nucleosome dyad, thereby facilitating symmetrical access to both H3K4 substrates within the NCP. Our study sheds light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity. | |||||||||
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 | 6pwx.cif.gz | 439.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6pwx.ent.gz | 311.9 KB | Display | PDB format |
PDBx/mmJSON format | 6pwx.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6pwx_validation.pdf.gz | 780.8 KB | Display | wwPDB validaton report |
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Full document | 6pwx_full_validation.pdf.gz | 811.4 KB | Display | |
Data in XML | 6pwx_validation.xml.gz | 47.1 KB | Display | |
Data in CIF | 6pwx_validation.cif.gz | 72.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pw/6pwx ftp://data.pdbj.org/pub/pdb/validation_reports/pw/6pwx | HTTPS FTP |
-Related structure data
Related structure data | 20514MC 6pwvC 6pwwC 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
-Protein , 5 types, 9 molecules AGKHLIMJN
#1: Protein | Mass: 59179.359 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RBBP5, RBQ3 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15291 | ||||||
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#2: 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 #3: Protein | Mass: 11394.426 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 #4: Protein | Mass: 13978.241 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 #5: 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 |
-DNA chain , 2 types, 2 molecules OP
#6: DNA chain | Mass: 45138.770 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#7: DNA chain | Mass: 45610.043 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-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: RbBP5 in complex with the nucleosome / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Xenopus laevis (African clawed frog) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
Vitrification | Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
-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: OTHER |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 64 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 32563 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Refine LS restraints |
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