+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26454 | |||||||||
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Title | Complex between MLL1-WRAD and an H2B-ubiquitinated nucleosome | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / endosomal transport / histone methyltransferase complex / regulation of tubulin deacetylation ...MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / endosomal transport / histone methyltransferase complex / regulation of tubulin deacetylation / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / hemopoiesis / regulation of embryonic development / MLL1 complex / histone acetyltransferase complex / positive regulation of gluconeogenesis / methylated histone binding / transcription initiation-coupled chromatin remodeling / skeletal system development / gluconeogenesis / Deactivation of the beta-catenin transactivating complex / Formation of the beta-catenin:TCF transactivating complex / trans-Golgi network / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / euchromatin / mitotic spindle / PKMTs methylate histone lysines / beta-catenin binding / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / response to estrogen / structural constituent of chromatin / nucleosome / nucleosome assembly / Neddylation / HATs acetylate histones / histone binding / regulation of cell cycle / transcription cis-regulatory region binding / protein heterodimerization activity / DNA damage response / 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 / nucleoplasm / identical protein binding / nucleus / metal ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Xenopus laevis (African clawed frog) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.25 Å | |||||||||
Authors | Niklas HA / Rahman S / Worden EJ / Wolberger C | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Multistate structures of the MLL1-WRAD complex bound to H2B-ubiquitinated nucleosome. Authors: Sanim Rahman / Niklas A Hoffmann / Evan J Worden / Marissa L Smith / Kevin E W Namitz / Bruce A Knutson / Michael S Cosgrove / Cynthia Wolberger / Abstract: The human Mixed Lineage Leukemia-1 (MLL1) complex methylates histone H3K4 to promote transcription and is stimulated by monoubiquitination of histone H2B. Recent structures of the MLL1-WRAD core ...The human Mixed Lineage Leukemia-1 (MLL1) complex methylates histone H3K4 to promote transcription and is stimulated by monoubiquitination of histone H2B. Recent structures of the MLL1-WRAD core complex, which comprises the MLL1 methyltransferase, DR5, bBp5, sh2L, and PY-30, have revealed variability in the docking of MLL1-WRAD on nucleosomes. In addition, portions of the Ash2L structure and the position of DPY30 remain ambiguous. We used an integrated approach combining cryoelectron microscopy (cryo-EM) and mass spectrometry cross-linking to determine a structure of the MLL1-WRAD complex bound to ubiquitinated nucleosomes. The resulting model contains the Ash2L intrinsically disordered region (IDR), SPRY insertion region, Sdc1-DPY30 interacting region (SDI-motif), and the DPY30 dimer. We also resolved three additional states of MLL1-WRAD lacking one or more subunits, which may reflect different steps in the assembly of MLL1-WRAD. The docking of subunits in all four states differs from structures of MLL1-WRAD bound to unmodified nucleosomes, suggesting that H2B-ubiquitin favors assembly of the active complex. Our results provide a more complete picture of MLL1-WRAD and the role of ubiquitin in promoting formation of the active methyltransferase complex. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26454.map.gz | 8.6 MB | EMDB map data format | |
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Header (meta data) | emd-26454-v30.xml emd-26454.xml | 32.2 KB 32.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26454_fsc.xml | 10.7 KB | Display | FSC data file |
Images | emd_26454.png | 81.9 KB | ||
Masks | emd_26454_msk_1.map | 103 MB | Mask map | |
Others | emd_26454_additional_1.map.gz emd_26454_half_map_1.map.gz emd_26454_half_map_2.map.gz | 80.8 MB 81.1 MB 81 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26454 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26454 | HTTPS FTP |
-Validation report
Summary document | emd_26454_validation.pdf.gz | 790.3 KB | Display | EMDB validaton report |
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Full document | emd_26454_full_validation.pdf.gz | 789.9 KB | Display | |
Data in XML | emd_26454_validation.xml.gz | 17.9 KB | Display | |
Data in CIF | emd_26454_validation.cif.gz | 23.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26454 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26454 | HTTPS FTP |
-Related structure data
Related structure data | 7ud5MC 8du4C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26454.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.058 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_26454_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_26454_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_26454_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_26454_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : MLL1 WRAD complex bound to the ubiquitinated nucleosome
+Supramolecule #1: MLL1 WRAD complex bound to the ubiquitinated nucleosome
+Supramolecule #2: MLL1 WRAD complex
+Supramolecule #3: nucleosome
+Macromolecule #1: Histone H3
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A
+Macromolecule #4: Histone H2B 1.1
+Macromolecule #7: cDNA FLJ56846, highly similar to Zinc finger protein HRX
+Macromolecule #8: WD repeat-containing protein 5
+Macromolecule #9: Set1/Ash2 histone methyltransferase complex subunit ASH2
+Macromolecule #10: Retinoblastoma-binding protein 5
+Macromolecule #11: Polyubiquitin-B
+Macromolecule #12: Protein dpy-30 homolog
+Macromolecule #5: 601 DNA (146-MER)
+Macromolecule #6: 601 DNA (146-MER)
+Macromolecule #13: S-ADENOSYL-L-HOMOCYSTEINE
+Macromolecule #14: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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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) / Number real images: 5091 / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |