+Open data
-Basic information
Entry | Database: PDB / ID: 7k6p | |||||||||
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Title | Active state Dot1 bound to the unacetylated H4 nucleosome | |||||||||
Components |
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Keywords | Structural Protein/DNA/Transferase / TRANSFERASE / Structural Protein-DNA-Transferase complex | |||||||||
Function / homology | Function and homology information negative regulation of heterochromatin formation / PKMTs methylate histone lysines / meiotic recombination checkpoint signaling / histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / global genome nucleotide-excision repair / postreplication repair / recombinational repair / mitotic intra-S DNA damage checkpoint signaling ...negative regulation of heterochromatin formation / PKMTs methylate histone lysines / meiotic recombination checkpoint signaling / histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / global genome nucleotide-excision repair / postreplication repair / recombinational repair / mitotic intra-S DNA damage checkpoint signaling / mitotic G1 DNA damage checkpoint signaling / subtelomeric heterochromatin formation / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / 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 / 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 / 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 / Translesion synthesis by POLK / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / EGFR downregulation / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / Josephin domain DUBs / Regulation of activated PAK-2p34 by proteasome mediated degradation / InlB-mediated entry of Listeria monocytogenes into host cell / IKK complex recruitment mediated by RIP1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / DNA damage checkpoint signaling / TNFR1-induced NF-kappa-B signaling pathway / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / Regulation of NF-kappa B signaling / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / activated TAK1 mediates p38 MAPK activation / Vpu mediated degradation of CD4 / Assembly of the pre-replicative complex / Negative regulators of DDX58/IFIH1 signaling / Deactivation of the beta-catenin transactivating complex / Degradation of DVL / CDK-mediated phosphorylation and removal of Cdc6 / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / nucleotide-excision repair / Regulation of signaling by CBL / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Fanconi Anemia Pathway / Hh mutants are degraded by ERAD / Negative regulation of FGFR3 signaling / SCF(Skp2)-mediated degradation of p27/p21 / Degradation of AXIN Similarity search - Function | |||||||||
Biological species | Xenopus laevis (African clawed frog) Saccharomyces cerevisiae (brewer's yeast) Homo sapiens (human) synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Valencia-Sanchez, M.I. / De Ioannes, P.E. / Miao, W. / Truong, D.M. / Lee, R. / Armache, J.-P. / Boeke, J.D. / Armache, K.-J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Science / Year: 2021 Title: Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation. Authors: Marco Igor Valencia-Sánchez / Pablo De Ioannes / Miao Wang / David M Truong / Rachel Lee / Jean-Paul Armache / Jef D Boeke / Karim-Jean Armache / Abstract: Dot1 (disruptor of telomeric silencing-1), the histone H3 lysine 79 (H3K79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias. Here, we provide ...Dot1 (disruptor of telomeric silencing-1), the histone H3 lysine 79 (H3K79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias. Here, we provide evidence that acetylation of histone H4 allosterically stimulates yeast Dot1 in a manner distinct from but coordinating with histone H2B ubiquitination (H2BUb). We further demonstrate that this stimulatory effect is specific to acetylation of lysine 16 (H4K16ac), a modification central to chromatin structure. We provide a mechanism of this histone cross-talk and show that H4K16ac and H2BUb play crucial roles in H3K79 di- and trimethylation in vitro and in vivo. These data reveal mechanisms that control H3K79 methylation and demonstrate how H4K16ac, H3K79me, and H2BUb function together to regulate gene transcription and gene silencing to ensure optimal maintenance and propagation of an epigenetic state. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7k6p.cif.gz | 366.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7k6p.ent.gz | 275.2 KB | Display | PDB format |
PDBx/mmJSON format | 7k6p.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7k6p_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7k6p_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7k6p_validation.xml.gz | 52 KB | Display | |
Data in CIF | 7k6p_validation.cif.gz | 80.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k6/7k6p ftp://data.pdbj.org/pub/pdb/validation_reports/k6/7k6p | HTTPS FTP |
-Related structure data
Related structure data | 22691MC 7k6qC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 6 types, 10 molecules AEBFCGDHKL
#1: Protein | Mass: 11562.554 Da / Num. of mol.: 2 / Mutation: K79M, G103A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P84233 #2: Protein | Mass: 10175.951 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P62799 #3: Protein | Mass: 11694.650 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P06897 #4: Protein | Mass: 10322.814 Da / Num. of mol.: 2 / Mutation: K120C,S32T Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P02281 #7: Protein | | Mass: 46686.094 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Saccharomyces cerevisiae (brewer's yeast) Production host: Escherichia coli (E. coli) References: UniProt: Q04089, [histone H3]-lysine79 N-trimethyltransferase #8: Protein | | Mass: 8622.922 Da / Num. of mol.: 1 / Mutation: G76C Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UBC / Production host: Escherichia coli (E. coli) / References: UniProt: P0CG48 |
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-DNA chain , 2 types, 2 molecules IJ
#5: DNA chain | Mass: 44824.570 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#6: DNA chain | Mass: 45304.863 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-Non-polymers , 1 types, 1 molecules
#9: Chemical | ChemComp-SAM / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7 | ||||||||||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.45 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 297 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 2400 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 8 sec. / Electron dose: 52 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 4031 |
EM imaging optics | Energyfilter slit width: 20 eV |
Image scans | Sampling size: 5 µm |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1673215 | ||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 473290 / Algorithm: BACK PROJECTION / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1 / Source name: PDB / Type: experimental model
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