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Yorodumi- PDB-6w5i: Cryo-EM structure of MLL1 in complex with RbBP5, WDR5, SET1, and ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6w5i | |||||||||
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Title | Cryo-EM structure of MLL1 in complex with RbBP5, WDR5, SET1, and ASH2L bound to the nucleosome (Class01) | |||||||||
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 / regulation of short-term neuronal synaptic plasticity / MLL3/4 complex / Set1C/COMPASS complex ...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 / regulation of short-term neuronal synaptic plasticity / MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / definitive hemopoiesis / NSL complex / histone H3K4 methyltransferase activity / T-helper 2 cell differentiation / : / Cardiogenesis / embryonic hemopoiesis / exploration behavior / anterior/posterior pattern specification / histone methyltransferase complex / regulation of tubulin deacetylation / : / regulation of cell division / Formation of WDR5-containing histone-modifying complexes / minor groove of adenine-thymine-rich DNA binding / membrane depolarization / MLL1 complex / regulation of embryonic development / hemopoiesis / histone acetyltransferase complex / negative regulation of fibroblast proliferation / homeostasis of number of cells within a tissue / positive regulation of gluconeogenesis / spleen development / transcription initiation-coupled chromatin remodeling / cellular response to transforming growth factor beta stimulus / methylated histone binding / Transferases; Transferring one-carbon groups; Methyltransferases / post-embryonic development / skeletal system development / Deactivation of the beta-catenin transactivating complex / gluconeogenesis / Formation of the beta-catenin:TCF transactivating complex / circadian regulation of gene expression / protein modification process / lysine-acetylated histone binding / euchromatin / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / visual learning / mitotic spindle / PKMTs methylate histone lysines / RMTs methylate histone arginines / beta-catenin binding / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / response to estrogen / nucleosome / Neddylation / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / histone binding / fibroblast proliferation / protein-containing complex assembly / transcription cis-regulatory region binding / regulation of cell cycle / protein heterodimerization activity / apoptotic process / DNA damage response / chromatin binding / positive regulation of cell population proliferation / nucleolus / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / 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 / metal ion binding / nucleus / 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: 6.9 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 | 6w5i.cif.gz | 595.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6w5i.ent.gz | 430 KB | Display | PDB format |
PDBx/mmJSON format | 6w5i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w5/6w5i ftp://data.pdbj.org/pub/pdb/validation_reports/w5/6w5i | HTTPS FTP |
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-Related structure data
Related structure data | 21542MC 6w5mC 6w5nC 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 , 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: 14250.499 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: hist1h2aj, h2ac14, LOC494591, XELAEV_18003602mg / Production host: Escherichia coli (E. coli) / References: UniProt: Q6AZJ8 #8: Protein | Mass: 13524.752 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 FIELDBright-field microscopy |
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: 6.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 13086 / 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: 355.17 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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