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Yorodumi- PDB-6w5n: Cryo-EM structure of MLL1 in complex with RbBP5, WDR5, SET1, and ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6w5n | |||||||||
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Title | Cryo-EM structure of MLL1 in complex with RbBP5, WDR5, SET1, and ASH2L bound to the nucleosome (Class05) | |||||||||
Components |
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Keywords | TRANSFERASE/STRUCTURAL PROTEIN/DNA / MLL1-NCP / H3K4 methylation / TRANSFERASE / TRANSFERASE-STRUCTURAL PROTEIN-DNA complex | |||||||||
Function / homology | Function and homology information protein-cysteine methyltransferase activity / response to potassium ion / [histone H3]-lysine4 N-methyltransferase / histone H3K4 monomethyltransferase activity / unmethylated CpG binding / histone H3K4 trimethyltransferase activity / negative regulation of DNA methylation-dependent heterochromatin formation / T-helper 2 cell differentiation / MLL3/4 complex / regulation of short-term neuronal synaptic plasticity ...protein-cysteine methyltransferase activity / response to potassium ion / [histone H3]-lysine4 N-methyltransferase / histone H3K4 monomethyltransferase activity / unmethylated CpG binding / histone H3K4 trimethyltransferase activity / negative regulation of DNA methylation-dependent heterochromatin formation / T-helper 2 cell differentiation / MLL3/4 complex / regulation of short-term neuronal synaptic plasticity / Set1C/COMPASS complex / MLL1/2 complex / definitive hemopoiesis / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / embryonic hemopoiesis / Cardiogenesis / anterior/posterior pattern specification / exploration behavior / regulation of tubulin deacetylation / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / hemopoiesis / minor groove of adenine-thymine-rich DNA binding / membrane depolarization / regulation of embryonic development / MLL1 complex / histone acetyltransferase complex / negative regulation of fibroblast proliferation / homeostasis of number of cells within a tissue / positive regulation of gluconeogenesis / spleen development / cellular response to transforming growth factor beta stimulus / methylated histone binding / transcription initiation-coupled chromatin remodeling / Transferases; Transferring one-carbon groups; Methyltransferases / post-embryonic development / skeletal system development / gluconeogenesis / Deactivation of the beta-catenin transactivating complex / lysine-acetylated histone binding / circadian regulation of gene expression / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / visual learning / protein modification process / euchromatin / mitotic spindle / PKMTs methylate histone lysines / RMTs methylate histone arginines / beta-catenin binding / Activation of anterior HOX genes in hindbrain development during early embryogenesis / response to estrogen / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / nucleosome / nucleosome assembly / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / HATs acetylate histones / histone binding / fibroblast proliferation / protein-containing complex assembly / methylation / regulation of cell cycle / transcription cis-regulatory region binding / protein heterodimerization activity / DNA damage response / chromatin binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / nucleolus / apoptotic process / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / DNA binding / zinc ion binding / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol 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: 6 Å | |||||||||
Authors | Park, S.H. / Lee, Y.T. / Ayoub, A. / Dou, Y. / Cho, U. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Commun / Year: 2021 Title: Mechanism for DPY30 and ASH2L intrinsically disordered regions to modulate the MLL/SET1 activity on chromatin. Authors: Young-Tae Lee / Alex Ayoub / Sang-Ho Park / Liang Sha / Jing Xu / Fengbiao Mao / Wei Zheng / Yang Zhang / Uhn-Soo Cho / Yali Dou / Abstract: Recent cryo-EM structures show the highly dynamic nature of the MLL1-NCP (nucleosome core particle) interaction. Functional implication and regulation of such dynamics remain unclear. Here we show ...Recent cryo-EM structures show the highly dynamic nature of the MLL1-NCP (nucleosome core particle) interaction. Functional implication and regulation of such dynamics remain unclear. Here we show that DPY30 and the intrinsically disordered regions (IDRs) of ASH2L work together in restricting the rotational dynamics of the MLL1 complex on the NCP. We show that DPY30 binding to ASH2L leads to stabilization and integration of ASH2L IDRs into the MLL1 complex and establishes new ASH2L-NCP contacts. The significance of ASH2L-DPY30 interactions is demonstrated by requirement of both ASH2L IDRs and DPY30 for dramatic increase of processivity and activity of the MLL1 complex. This DPY30 and ASH2L-IDR dependent regulation is NCP-specific and applies to all members of the MLL/SET1 family of enzymes. We further show that DPY30 is causal for de novo establishment of H3K4me3 in ESCs. Our study provides a paradigm of how H3K4me3 is regulated on chromatin and how H3K4me3 heterogeneity can be modulated by ASH2L IDR interacting proteins. | |||||||||
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 | 6w5n.cif.gz | 602.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6w5n.ent.gz | 428.7 KB | Display | PDB format |
PDBx/mmJSON format | 6w5n.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6w5n_validation.pdf.gz | 868.2 KB | Display | wwPDB validaton report |
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Full document | 6w5n_full_validation.pdf.gz | 1000.5 KB | Display | |
Data in XML | 6w5n_validation.xml.gz | 76.8 KB | Display | |
Data in CIF | 6w5n_validation.cif.gz | 114.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w5/6w5n ftp://data.pdbj.org/pub/pdb/validation_reports/w5/6w5n | HTTPS FTP |
-Related structure data
Related structure data | 21544MC 6w5iC 6w5mC 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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-Components
-Protein , 8 types, 12 molecules ABCDGKHLIMJN
#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: 34390.992 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 | ||||||
#3: Protein | Mass: 24141.732 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: KMT2A, ALL1, CXXC7, HRX, HTRX, MLL, MLL1, TRX1 / Production host: Escherichia coli (E. coli) References: UniProt: Q03164, [histone H3]-lysine4 N-trimethyltransferase | ||||||
#4: Protein | Mass: 60244.641 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ASH2L, ASH2L1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UBL3 | ||||||
#5: 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 #6: 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 #7: 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 #8: 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
#9: DNA chain | Mass: 45138.770 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#10: 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 |
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Molecular weight | Value: 0.38 MDa / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
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: 6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 23236 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 363.71 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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