+Open data
-Basic information
Entry | Database: PDB / ID: 8du4 | ||||||
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Title | Complex between RbBP5-WDR5 and an H2B-ubiquitinated nucleosome | ||||||
Components |
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Keywords | DNA BINDING PROTEIN / ubiquitin / chromatin / MLL / methylation | ||||||
Function / homology | Function and homology information MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / regulation of tubulin deacetylation / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes ...MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / regulation of tubulin deacetylation / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / regulation of embryonic development / MLL1 complex / histone acetyltransferase complex / positive regulation of gluconeogenesis / methylated histone binding / transcription initiation-coupled chromatin remodeling / skeletal system development / gluconeogenesis / 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 / RMTs methylate histone arginines / mitotic spindle / Activation of anterior HOX genes in hindbrain development during early embryogenesis / response to estrogen / structural constituent of chromatin / nucleosome / nucleosome assembly / Neddylation / HATs acetylate histones / histone binding / transcription cis-regulatory region binding / regulation of cell cycle / protein heterodimerization activity / DNA damage response / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / regulation of DNA-templated transcription / nucleolus / negative regulation of transcription by RNA polymerase II / DNA binding / nucleoplasm / nucleus Similarity search - Function | ||||||
Biological species | Xenopus laevis (African clawed frog) synthetic construct (others) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.55 Å | ||||||
Authors | Niklas, H.A. / Rahman, S. / Worden, E.J. / Wolberger, C. | ||||||
Funding support | United States, 1items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Multistate structures of the MLL1-WRAD complex bound to H2B-ubiquitinated nucleosome. Authors: Sanim Rahman / Niklas A Hoffmann / Evan J Worden / Marissa L Smith / Kevin E W Namitz / Bruce A Knutson / Michael S Cosgrove / Cynthia Wolberger / Abstract: The human Mixed Lineage Leukemia-1 (MLL1) complex methylates histone H3K4 to promote transcription and is stimulated by monoubiquitination of histone H2B. Recent structures of the MLL1-WRAD core ...The human Mixed Lineage Leukemia-1 (MLL1) complex methylates histone H3K4 to promote transcription and is stimulated by monoubiquitination of histone H2B. Recent structures of the MLL1-WRAD core complex, which comprises the MLL1 methyltransferase, DR5, bBp5, sh2L, and PY-30, have revealed variability in the docking of MLL1-WRAD on nucleosomes. In addition, portions of the Ash2L structure and the position of DPY30 remain ambiguous. We used an integrated approach combining cryoelectron microscopy (cryo-EM) and mass spectrometry cross-linking to determine a structure of the MLL1-WRAD complex bound to ubiquitinated nucleosomes. The resulting model contains the Ash2L intrinsically disordered region (IDR), SPRY insertion region, Sdc1-DPY30 interacting region (SDI-motif), and the DPY30 dimer. We also resolved three additional states of MLL1-WRAD lacking one or more subunits, which may reflect different steps in the assembly of MLL1-WRAD. The docking of subunits in all four states differs from structures of MLL1-WRAD bound to unmodified nucleosomes, suggesting that H2B-ubiquitin favors assembly of the active complex. Our results provide a more complete picture of MLL1-WRAD and the role of ubiquitin in promoting formation of the active methyltransferase complex. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8du4.cif.gz | 454.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8du4.ent.gz | 349.4 KB | Display | PDB format |
PDBx/mmJSON format | 8du4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8du4_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8du4_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8du4_validation.xml.gz | 62.7 KB | Display | |
Data in CIF | 8du4_validation.cif.gz | 95.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/du/8du4 ftp://data.pdbj.org/pub/pdb/validation_reports/du/8du4 | HTTPS FTP |
-Related structure data
Related structure data | 27715MC 7ud5C 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 , 7 types, 11 molecules AEBFCGDHLNO
#1: Protein | Mass: 15383.028 Da / Num. of mol.: 2 / Mutation: K4Nle, M90Nle, M120Nle Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: XELAEV_18002543mg / Production host: Escherichia coli (E. coli) / References: UniProt: A0A310TTQ1 #2: 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 #3: Protein | Mass: 14109.436 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: hist1h2aj, LOC494591, XELAEV_18003602mg / Production host: Escherichia coli (E. coli) / References: UniProt: Q6AZJ8 #4: Protein | Mass: 13629.911 Da / Num. of mol.: 2 / Mutation: S32T, K120C 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 #7: Protein | | Mass: 36648.371 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WDR5, BIG3 / Production host: Escherichia coli (E. coli) / References: UniProt: P61964 #8: Protein | | Mass: 59223.477 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 #9: Protein | | Mass: 9164.521 Da / Num. of mol.: 1 / Mutation: G76C Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UBB / Production host: Escherichia coli (E. coli) / References: UniProt: J3QS39 |
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-601 DNA (146- ... , 2 types, 2 molecules IJ
#5: DNA chain | Mass: 44825.559 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
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#6: DNA chain | Mass: 45305.852 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
-Details
Has ligand of interest | N |
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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
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Source (recombinant) |
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Buffer solution | pH: 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: 2800 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 5091 |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.55 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 134528 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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