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Yorodumi- EMDB-31039: Yeast Set2 bound to a nucleosome containing oncohistone mutations -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31039 | ||||||||||||
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Title | Yeast Set2 bound to a nucleosome containing oncohistone mutations | ||||||||||||
Map data | |||||||||||||
Sample |
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Function / homology | Function and homology information [histone H3]-lysine36 N-trimethyltransferase / histone H3K36 methyltransferase activity / structural constituent of chromatin / nucleosome / chromosome / protein heterodimerization activity / regulation of DNA-templated transcription / DNA binding / nucleus Similarity search - Function | ||||||||||||
Biological species | Xenopus laevis (African clawed frog) / Saccharomyces cerevisiae (brewer's yeast) / synthetic construct (others) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
Authors | Jing H / Liu Y | ||||||||||||
Funding support | China, 3 items
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Citation | Journal: Cell Discov / Year: 2021 Title: Cryo-EM structure of SETD2/Set2 methyltransferase bound to a nucleosome containing oncohistone mutations. Authors: Yingying Liu / Yanjun Zhang / Han Xue / Mi Cao / Guohui Bai / Zongkai Mu / Yanli Yao / Shuyang Sun / Dong Fang / Jing Huang / Abstract: Substitution of lysine 36 with methionine in histone H3.3 (H3.3K36M) is an oncogenic mutation that inhibits SETD2-mediated histone H3K36 tri-methylation in tumors. To investigate how the oncohistone ...Substitution of lysine 36 with methionine in histone H3.3 (H3.3K36M) is an oncogenic mutation that inhibits SETD2-mediated histone H3K36 tri-methylation in tumors. To investigate how the oncohistone mutation affects the function of SETD2 at the nucleosome level, we determined the cryo-EM structure of human SETD2 associated with an H3.3K36M nucleosome and cofactor S-adenosylmethionine (SAM), and revealed that SETD2 is attached to the N-terminal region of histone H3 and the nucleosome DNA at superhelix location 1, accompanied with the partial unwrapping of nucleosome DNA to expose the SETD2-binding site. These structural features were also observed in the previous cryo-EM structure of the fungal Set2-nucleosome complex. By contrast with the stable association of SETD2 with the H3.3K36M nucleosome, the EM densities of SETD2 could not be observed on the wild-type nucleosome surface, suggesting that the association of SETD2 with wild-type nucleosome might be transient. The linker histone H1, which stabilizes the wrapping of nucleosome DNA at the entry/exit sites, exhibits an inhibitory effect on the activities of SETD2 and displays inversely correlated genome distributions with that of the H3K36me3 marks. Cryo-EM analysis of yeast H3K36 methyltransferase Set2 complexed with nucleosomes further revealed evolutionarily conserved structural features for nucleosome recognition in eukaryotes, and provides insights into the mechanism of activity regulation. These findings have advanced our understanding of the structural basis for the tumorigenesis mechanism of the H3.3K36M mutation and highlight the effect of nucleosome conformation on the regulation of histone 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_31039.map.gz | 49.4 MB | EMDB map data format | |
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Header (meta data) | emd-31039-v30.xml emd-31039.xml | 17 KB 17 KB | Display Display | EMDB header |
Images | emd_31039.png | 99.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31039 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31039 | HTTPS FTP |
-Validation report
Summary document | emd_31039_validation.pdf.gz | 464.4 KB | Display | EMDB validaton report |
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Full document | emd_31039_full_validation.pdf.gz | 463.9 KB | Display | |
Data in XML | emd_31039_validation.xml.gz | 5.9 KB | Display | |
Data in CIF | emd_31039_validation.cif.gz | 6.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31039 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31039 | HTTPS FTP |
-Related structure data
Related structure data | 7ea5MC 7ea8C 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_31039.map.gz / Format: CCP4 / Size: 52.7 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: 1.09 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : The Set2-nucleosome(H3K36M)complex structure
+Supramolecule #1: The Set2-nucleosome(H3K36M)complex structure
+Macromolecule #1: Histone H3
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A
+Macromolecule #4: Histone H2B
+Macromolecule #7: Histone-lysine N-methyltransferase, H3 lysine-36 specific
+Macromolecule #5: 601-DNA
+Macromolecule #6: 601-DNA
+Macromolecule #8: ZINC ION
+Macromolecule #9: S-ADENOSYLMETHIONINE
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.3 mg/mL |
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Buffer | pH: 7.5 |
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: 1.5625 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 |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 225474 |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |