+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9998 | |||||||||
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Title | Cryo-EM structure of human MLL1-ubNCP complex (3.2 angstrom) | |||||||||
Map data | Main map of MLL1-ubNCP (3.2 angstrom) | |||||||||
Sample |
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Keywords | histone modification / nucleosome / MLL / TRANSCRIPTION / TRANSCRIPTION-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 / Cardiogenesis / Formation of the ternary complex, and subsequently, the 43S complex / embryonic hemopoiesis / exploration behavior / anterior/posterior pattern specification / Ribosomal scanning and start codon recognition / regulation of tubulin deacetylation / histone methyltransferase complex / Translation initiation complex formation / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / SARS-CoV-1 modulates host translation machinery / minor groove of adenine-thymine-rich DNA binding / Peptide chain elongation / Selenocysteine synthesis / membrane depolarization / Formation of a pool of free 40S subunits / regulation of embryonic development / Eukaryotic Translation Termination / hemopoiesis / MLL1 complex / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / histone acetyltransferase complex / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / negative regulation of fibroblast proliferation / cytosolic ribosome / homeostasis of number of cells within a tissue / Maturation of protein E / Maturation of protein E / positive regulation of gluconeogenesis / spleen development / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / lysine-acetylated histone binding / cellular response to transforming growth factor beta stimulus / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / methylated histone binding / Downregulation of ERBB4 signaling / NOTCH3 Activation and Transmission of Signal to the Nucleus / APC-Cdc20 mediated degradation of Nek2A / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / PINK1-PRKN Mediated Mitophagy / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Regulation of pyruvate metabolism / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / Regulation of PTEN localization / transcription initiation-coupled chromatin remodeling / NRIF signals cell death from the nucleus / Regulation of BACH1 activity / Activated NOTCH1 Transmits Signal to the Nucleus / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by REV1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Xenopus laevis (African clawed frog) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Huang J / Xue H | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nature / Year: 2019 Title: Structural basis of nucleosome recognition and modification by MLL methyltransferases. Authors: Han Xue / Tonghui Yao / Mi Cao / Guanjun Zhu / Yan Li / Guiyong Yuan / Yong Chen / Ming Lei / Jing Huang / Abstract: Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and ...Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and distinct roles in the regulation of transcription in haematopoiesis, adipogenesis and development. The C-terminal catalytic SET (Su(var.)3-9, enhancer of zeste and trithorax) domains of MLL proteins are associated with a common set of regulatory factors (WDR5, RBBP5, ASH2L and DPY30) to achieve specific activities. Current knowledge of the regulation of MLL activity is limited to the catalysis of histone H3 peptides, and how H3K4 methyl marks are deposited on nucleosomes is poorly understood. H3K4 methylation is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120ub1), a prevalent histone H2B mark that disrupts chromatin compaction and favours open chromatin structures, but the underlying mechanism remains unknown. Here we report cryo-electron microscopy structures of human MLL1 and MLL3 catalytic modules associated with nucleosome core particles that contain H2BK120ub1 or unmodified H2BK120. These structures demonstrate that the MLL1 and MLL3 complexes both make extensive contacts with the histone-fold and DNA regions of the nucleosome; this allows ease of access to the histone H3 tail, which is essential for the efficient methylation of H3K4. The H2B-conjugated ubiquitin binds directly to RBBP5, orienting the association between MLL1 or MLL3 and the nucleosome. The MLL1 and MLL3 complexes display different structural organizations at the interface between the WDR5, RBBP5 and MLL1 (or the corresponding MLL3) subunits, which accounts for the opposite roles of WDR5 in regulating the activity of the two enzymes. These findings transform our understanding of the structural basis for the regulation of MLL activity at the nucleosome level, and highlight the pivotal role of nucleosome regulation in histone-tail modification. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9998.map.gz | 69.9 MB | EMDB map data format | |
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Header (meta data) | emd-9998-v30.xml emd-9998.xml | 34 KB 34 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_9998_fsc.xml | 9.6 KB | Display | FSC data file |
Images | emd_9998.png | 209.2 KB | ||
Masks | emd_9998_msk_1.map | 75.1 MB | Mask map | |
Filedesc metadata | emd-9998.cif.gz | 7.9 KB | ||
Others | emd_9998_additional_1.map.gz emd_9998_additional_2.map.gz emd_9998_additional_3.map.gz emd_9998_additional_4.map.gz | 70 MB 70 MB 69.9 MB 69.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9998 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9998 | HTTPS FTP |
-Validation report
Summary document | emd_9998_validation.pdf.gz | 631.8 KB | Display | EMDB validaton report |
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Full document | emd_9998_full_validation.pdf.gz | 631.3 KB | Display | |
Data in XML | emd_9998_validation.xml.gz | 11.1 KB | Display | |
Data in CIF | emd_9998_validation.cif.gz | 14.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9998 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9998 | HTTPS FTP |
-Related structure data
Related structure data | 6kiuMC 0693C 0694C 0695C 9999C 6kivC 6kiwC 6kixC 6kizC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9998.map.gz / Format: CCP4 / Size: 75.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Main map of MLL1-ubNCP (3.2 angstrom) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.09 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_9998_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Additional map showing good density of RBBP5 AS
File | emd_9998_additional_1.map | ||||||||||||
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Annotation | Additional map showing good density of RBBP5_AS | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Additional map showing good density of MLL1 AS
File | emd_9998_additional_2.map | ||||||||||||
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Annotation | Additional map showing good density of MLL1_AS | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Additional map showing good density of H2BK120ub1
File | emd_9998_additional_3.map | ||||||||||||
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Annotation | Additional map showing good density of H2BK120ub1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Additional map showing good density of ASH2L SPRY
File | emd_9998_additional_4.map | ||||||||||||
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Annotation | Additional map showing good density of ASH2L_SPRY | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Human MLL1 complex associated with an H2B-monoubiquitinated nucle...
+Supramolecule #1: Human MLL1 complex associated with an H2B-monoubiquitinated nucle...
+Supramolecule #2: Human MLL1
+Supramolecule #3: H2B-monoubiquitinated nucleosome
+Macromolecule #1: Histone H3
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A
+Macromolecule #4: Histone H2B 1.1
+Macromolecule #7: Histone-lysine N-methyltransferase 2A
+Macromolecule #8: Retinoblastoma-binding protein 5
+Macromolecule #9: WD repeat-containing protein 5
+Macromolecule #10: Set1/Ash2 histone methyltransferase complex subunit ASH2
+Macromolecule #11: Ubiquitin
+Macromolecule #5: DNA (145-MER)
+Macromolecule #6: DNA (145-MER)
+Macromolecule #12: S-ADENOSYL-L-HOMOCYSTEINE
+Macromolecule #13: ZINC ION
+Macromolecule #14: LYSINE
+Macromolecule #15: GLUTAMINE
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |