+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 / 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 / Formation of the ternary complex, and subsequently, the 43S complex / embryonic hemopoiesis / exploration behavior / anterior/posterior pattern specification / Translation initiation complex formation / Ribosomal scanning and start codon recognition / histone methyltransferase complex / regulation of tubulin deacetylation / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / minor groove of adenine-thymine-rich DNA binding / membrane depolarization / Selenocysteine synthesis / Formation of a pool of free 40S subunits / regulation of embryonic development / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / hemopoiesis / MLL1 complex / SRP-dependent cotranslational protein targeting to membrane / transcription factor TFIID complex / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Viral mRNA Translation / RNA polymerase II general transcription initiation factor activity / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / histone acetyltransferase complex / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / cytosolic ribosome / negative regulation of fibroblast proliferation / Maturation of protein E / Maturation of protein E / homeostasis of number of cells within a tissue / ER Quality Control Compartment (ERQC) / positive regulation of gluconeogenesis / spleen development / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / transcription initiation-coupled chromatin remodeling / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / cellular response to transforming growth factor beta stimulus / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / 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 / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / methylated histone binding / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / NRIF signals cell death from the nucleus / Regulation of PTEN localization / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of BACH1 activity / Translesion synthesis by REV1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by POLK / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling 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) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |