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Yorodumi- EMDB-31040: Human SETD2 bound to a nucleosome containing oncohistone mutations -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31040 | ||||||||||||
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Title | Human SETD2 bound to a nucleosome containing oncohistone mutations | ||||||||||||
Map data | main map | ||||||||||||
Sample |
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Keywords | SETD2 / methyltransferase / nucleosome / H3.3K36M / GENE REGULATION | ||||||||||||
Function / homology | Function and homology information mesoderm morphogenesis / coronary vasculature morphogenesis / morphogenesis of a branching structure / peptidyl-lysine trimethylation / cell migration involved in vasculogenesis / microtubule cytoskeleton organization involved in mitosis / [histone H3]-lysine36 N-trimethyltransferase / histone H3K36 trimethyltransferase activity / embryonic placenta morphogenesis / regulation of mRNA export from nucleus ...mesoderm morphogenesis / coronary vasculature morphogenesis / morphogenesis of a branching structure / peptidyl-lysine trimethylation / cell migration involved in vasculogenesis / microtubule cytoskeleton organization involved in mitosis / [histone H3]-lysine36 N-trimethyltransferase / histone H3K36 trimethyltransferase activity / embryonic placenta morphogenesis / regulation of mRNA export from nucleus / pericardium development / stem cell development / nucleosome organization / histone H3K36 methyltransferase activity / protein-lysine N-methyltransferase activity / response to type I interferon / positive regulation of ossification / embryonic cranial skeleton morphogenesis / response to alkaloid / regulation of protein localization to chromatin / response to metal ion / histone H3 methyltransferase activity / regulation of double-strand break repair via homologous recombination / endodermal cell differentiation / alpha-tubulin binding / positive regulation of interferon-alpha production / mismatch repair / positive regulation of autophagy / Replacement of protamines by nucleosomes in the male pronucleus / heterochromatin organization / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / forebrain development / nucleosomal DNA binding / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / RNA Polymerase I Promoter Opening / Assembly of the ORC complex at the origin of replication / Transferases; Transferring one-carbon groups; Methyltransferases / DNA methylation / Condensation of Prophase Chromosomes / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / regulation of cytokinesis / PRC2 methylates histones and DNA / innate immune response in mucosa / Defective pyroptosis / neural tube closure / HDACs deacetylate histones / transcription elongation by RNA polymerase II / stem cell differentiation / RNA Polymerase I Promoter Escape / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / B-WICH complex positively regulates rRNA expression / G2/M DNA damage checkpoint / response to organic cyclic compound / DNA Damage/Telomere Stress Induced Senescence / Metalloprotease DUBs / PKMTs methylate histone lysines / Meiotic recombination / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / antimicrobial humoral immune response mediated by antimicrobial peptide / UCH proteinases / nucleosome / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromosome / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / Processing of DNA double-strand break ends / antibacterial humoral response / Senescence-Associated Secretory Phenotype (SASP) / regulation of gene expression / angiogenesis / Oxidative Stress Induced Senescence / defense response to virus / Estrogen-dependent gene expression / Ub-specific processing proteases / defense response to Gram-positive bacterium / protein heterodimerization activity / Amyloid fiber formation / regulation of DNA-templated transcription / DNA binding / extracellular space Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 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_31040.map.gz | 49.4 MB | EMDB map data format | |
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Header (meta data) | emd-31040-v30.xml emd-31040.xml | 18.8 KB 18.8 KB | Display Display | EMDB header |
Images | emd_31040.png | 223.1 KB | ||
Filedesc metadata | emd-31040.cif.gz | 6.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31040 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31040 | HTTPS FTP |
-Validation report
Summary document | emd_31040_validation.pdf.gz | 570.5 KB | Display | EMDB validaton report |
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Full document | emd_31040_full_validation.pdf.gz | 570 KB | Display | |
Data in XML | emd_31040_validation.xml.gz | 5.9 KB | Display | |
Data in CIF | emd_31040_validation.cif.gz | 6.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31040 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31040 | HTTPS FTP |
-Related structure data
Related structure data | 7ea8MC 7ea5C 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_31040.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | main map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 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 : Human SETD2-NCP(H3.3K36M)-SAM complex structure
+Supramolecule #1: Human SETD2-NCP(H3.3K36M)-SAM complex structure
+Supramolecule #2: Histone-lysine N-methyltransferase SETD2
+Supramolecule #3: Histone
+Supramolecule #4: DNA
+Macromolecule #1: Histone-lysine N-methyltransferase SETD2
+Macromolecule #2: Histone H3.3
+Macromolecule #3: Histone H4
+Macromolecule #4: Histone H2A type 1-D
+Macromolecule #5: Histone H2B type 2-E
+Macromolecule #6: 601-DNA
+Macromolecule #7: 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
Startup model | Type of model: EMDB MAP |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 154984 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |