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Open data
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Basic information
Entry | Database: PDB / ID: 6pwv | |||||||||
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Title | Cryo-EM structure of MLL1 core complex bound to the nucleosome | |||||||||
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![]() | HISTONE BINDING/DNA BINDING/DNA / Mixed-Lineage Leukemia / MLL1 / nucleosome / histone H3 Lys4 methyltransferase / RbBP5 / WDR5 / HISTONE BINDING-DNA BINDING-DNA complex | |||||||||
Function / homology | ![]() 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 / MLL3/4 complex / regulation of short-term neuronal synaptic plasticity / 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 / MLL3/4 complex / regulation of short-term neuronal synaptic plasticity / Set1C/COMPASS complex / MLL1/2 complex / T-helper 2 cell differentiation / definitive hemopoiesis / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / embryonic hemopoiesis / exploration behavior / anterior/posterior pattern specification / endosomal transport / histone methyltransferase complex / regulation of tubulin deacetylation / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / minor groove of adenine-thymine-rich DNA binding / membrane depolarization / regulation of embryonic development / hemopoiesis / MLL1 complex / transcription factor TFIID complex / RNA polymerase II general transcription initiation factor activity / 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 / gluconeogenesis / Deactivation of the beta-catenin transactivating complex / Formation of the beta-catenin:TCF transactivating complex / circadian regulation of gene expression / euchromatin / lysine-acetylated histone binding / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / visual learning / protein modification process / trans-Golgi network / mitotic spindle / PKMTs methylate histone lysines / beta-catenin binding / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Transcriptional regulation of granulopoiesis / response to estrogen / 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 / methylation / 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 / regulation of DNA-templated transcription / nucleolus / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / Golgi apparatus / 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 | ![]() ![]() synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.2 Å | |||||||||
![]() | 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 | ![]() ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 649 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 985.6 KB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 80.6 KB | Display | |
Data in CIF | ![]() | 122.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 20512MC ![]() 6pwwC ![]() 6pwxC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 9 types, 14 molecules ABCGKHLIMJNEFD
#1: Protein | Mass: 59179.359 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||||||||||
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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.) ![]() ![]() ![]() | ||||||||||
#3: Protein | Mass: 24141.732 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q03164, histone-lysine N-methyltransferase | ||||||||||
#4: Protein | Mass: 15435.126 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #5: Protein | Mass: 11394.426 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #6: Protein | Mass: 13978.241 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #7: Protein | Mass: 13524.752 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #10: Protein | Mass: 11492.876 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #11: Protein | | Mass: 60244.641 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-DNA chain , 2 types, 2 molecules OP
#8: DNA chain | Mass: 45138.770 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#9: DNA chain | Mass: 45610.043 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-Non-polymers , 2 types, 4 molecules ![](data/chem/img/SAH.gif)
![](data/chem/img/ZN.gif)
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#12: Chemical | #13: Chemical | |
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-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
Component | Name: Human MLL1 complex bound to the nucleosome / Type: COMPLEX / Entity ID: #1-#11 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
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 |
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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: 64 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING ONLY |
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Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 6.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 8433 / Symmetry type: POINT |