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Yorodumi- EMDB-9844: cryo-EM structure of DOT1L bound to H2B ubiquitinated nucleosome -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9844 | ||||||||||||
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Title | cryo-EM structure of DOT1L bound to H2B ubiquitinated nucleosome | ||||||||||||
Map data | catalytic domain of DOT1L bound to H2B ubiquitinated nucleosome. | ||||||||||||
Sample |
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Keywords | histone / nucleosome / methylation / GENE REGULATION | ||||||||||||
Function / homology | Function and homology information histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / regulation of transcription regulatory region DNA binding / hypothalamus gonadotrophin-releasing hormone neuron development / histone H3 methyltransferase activity / regulation of receptor signaling pathway via JAK-STAT / female meiosis I / positive regulation of protein monoubiquitination / mitochondrion transport along microtubule ...histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / regulation of transcription regulatory region DNA binding / hypothalamus gonadotrophin-releasing hormone neuron development / histone H3 methyltransferase activity / regulation of receptor signaling pathway via JAK-STAT / female meiosis I / positive regulation of protein monoubiquitination / mitochondrion transport along microtubule / fat pad development / female gonad development / histone methyltransferase activity / seminiferous tubule development / male meiosis I / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / regulation of neuron apoptotic process / regulation of proteasomal protein catabolic process / energy homeostasis / 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 / telomere organization / 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 / neuron projection morphogenesis / 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 / regulation of mitochondrial membrane potential / 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 / positive regulation of protein ubiquitination / 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 / NOTCH3 Activation and Transmission of Signal to the Nucleus / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A Similarity search - Function | ||||||||||||
Biological species | Xenopus laevis (African clawed frog) / synthetic construct (others) / Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.8 Å | ||||||||||||
Authors | Jang S / Song JJ | ||||||||||||
Funding support | Korea, Republic Of, 3 items
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Citation | Journal: Genes Dev / Year: 2019 Title: Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase. Authors: Seongmin Jang / Chanshin Kang / Han-Sol Yang / Taeyang Jung / Hans Hebert / Ka Young Chung / Seung Joong Kim / Sungchul Hohng / Ji-Joon Song / Abstract: DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we ...DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we present cryo-EM structures of DOT1L complexes with unmodified or H2B ubiquitinated nucleosomes, showing that DOT1L recognizes H2B ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L, respectively. Furthermore, the structures combined with single-molecule FRET experiments show that H2B ubiquitination enhances a noncatalytic function of the DOT1L-destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L. | ||||||||||||
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_9844.map.gz | 37.9 MB | EMDB map data format | |
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Header (meta data) | emd-9844-v30.xml emd-9844.xml | 17.6 KB 17.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_9844_fsc.xml | 8 KB | Display | FSC data file |
Images | emd_9844.png | 112.4 KB | ||
Filedesc metadata | emd-9844.cif.gz | 6.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9844 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9844 | HTTPS FTP |
-Related structure data
Related structure data | 6jmaMC 9843C 6jm9C C: citing same article (ref.) M: atomic model generated by this map |
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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_9844.map.gz / Format: CCP4 / Size: 40.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | catalytic domain of DOT1L bound to H2B ubiquitinated nucleosome. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 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 : DOT1L bound to H2B ubiquitinated nucleosome
Entire | Name: DOT1L bound to H2B ubiquitinated nucleosome |
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Components |
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-Supramolecule #1: DOT1L bound to H2B ubiquitinated nucleosome
Supramolecule | Name: DOT1L bound to H2B ubiquitinated nucleosome / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#7 |
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Source (natural) | Organism: Xenopus laevis (African clawed frog) |
Molecular weight | Theoretical: 290 KDa |
-Macromolecule #1: DNA I&J
Macromolecule | Name: DNA I&J / type: dna / ID: 1 / Number of copies: 2 / Classification: DNA |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 35.168547 KDa |
Sequence | String: (DA)(DG)(DA)(DT)(DT)(DC)(DT)(DA)(DC)(DC) (DA)(DA)(DA)(DA)(DG)(DT)(DG)(DT)(DA)(DT) (DT)(DT)(DG)(DG)(DA)(DA)(DA)(DC)(DT) (DG)(DC)(DT)(DC)(DC)(DA)(DT)(DC)(DA)(DA) (DA) (DA)(DG)(DG)(DC)(DA)(DT) ...String: (DA)(DG)(DA)(DT)(DT)(DC)(DT)(DA)(DC)(DC) (DA)(DA)(DA)(DA)(DG)(DT)(DG)(DT)(DA)(DT) (DT)(DT)(DG)(DG)(DA)(DA)(DA)(DC)(DT) (DG)(DC)(DT)(DC)(DC)(DA)(DT)(DC)(DA)(DA) (DA) (DA)(DG)(DG)(DC)(DA)(DT)(DG)(DT) (DT)(DC)(DA)(DG)(DC)(DT)(DG)(DA)(DA)(DT) (DT)(DC) (DA)(DG)(DC)(DT)(DG)(DA)(DA) (DC)(DA)(DT)(DG)(DC)(DC)(DT)(DT)(DT)(DT) (DG)(DA)(DT) (DG)(DG)(DA)(DG)(DC)(DA) (DG)(DT)(DT)(DT)(DC)(DC)(DA)(DA)(DA)(DT) (DA)(DC)(DA)(DC) (DT)(DT)(DT)(DT)(DG) (DG)(DT)(DA)(DG)(DA)(DA)(DT)(DC)(DT) |
-Macromolecule #2: Histone H3.2
Macromolecule | Name: Histone H3.2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Xenopus laevis (African clawed frog) |
Molecular weight | Theoretical: 11.48841 KDa |
Recombinant expression | Organism: Escherichia coli BL21 (bacteria) |
Sequence | String: PHRYRPGTVA LREIRRYQKS TELLIRKLPF QRLVREIAQD FKTDLRFQSS AVMALQEASE AYLVGLFEDT NLCAIHAKRV TIMPKDIQL ARRIRGERA UniProtKB: Histone H3.2 |
-Macromolecule #3: Histone H4
Macromolecule | Name: Histone H4 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Xenopus laevis (African clawed frog) |
Molecular weight | Theoretical: 9.99077 KDa |
Recombinant expression | Organism: Escherichia coli BL21 (bacteria) |
Sequence | String: KRHRKVLRDN IQGITKPAIR RLARRGGVKR ISGLIYEETR GVLKVFLENV IRDAVTYTEH AKRKTVTAMD VVYALKRQGR TLYGFGG UniProtKB: Histone H4 |
-Macromolecule #4: Histone H2A
Macromolecule | Name: Histone H2A / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Xenopus laevis (African clawed frog) |
Molecular weight | Theoretical: 12.660719 KDa |
Recombinant expression | Organism: Escherichia coli BL21 (bacteria) |
Sequence | String: AKTRSSRAGL QFPVGRVHRL LRKGNYAERV GAGAPVYLAA VLEYLTAEIL ELAGNAARDN KKTRIIPRHL QLAVRNDEEL NKLLGRVTI AQGGVLPNIQ SVLLPKKTES SKSAKSK UniProtKB: Histone H2A |
-Macromolecule #5: Histone H2B 1.1
Macromolecule | Name: Histone H2B 1.1 / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Xenopus laevis (African clawed frog) |
Molecular weight | Theoretical: 10.478032 KDa |
Recombinant expression | Organism: Escherichia coli BL21 (bacteria) |
Sequence | String: TRKESYAIYV YKVLKQVHPD TGISSKAMSI MNSFVNDVFE RIAGEASRLA HYNKRSTITS REIQTAVRLL LPGELAKHAV SEGTKAVTK YTSAK UniProtKB: Histone H2B 1.1 |
-Macromolecule #6: Histone-lysine N-methyltransferase, H3 lysine-79 specific
Macromolecule | Name: Histone-lysine N-methyltransferase, H3 lysine-79 specific type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO / EC number: histone-lysine N-methyltransferase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 37.930039 KDa |
Recombinant expression | Organism: Escherichia coli BL21 (bacteria) |
Sequence | String: LELRLKSPVG AEPAVYPWPL PVYDKHHDAA HEIIETIRWV CEEIPDLKLA MENYVLIDYD TKSFESMQRL CDKYNRAIDS IHQLWKGTT QPMKLNTRPS TGLLRHILQQ VYNHSVTDPE KLNNYEPFSP EVYGETSFDL VAQMIDEIKM TDDDLFVDLG S GVGQVVLQ ...String: LELRLKSPVG AEPAVYPWPL PVYDKHHDAA HEIIETIRWV CEEIPDLKLA MENYVLIDYD TKSFESMQRL CDKYNRAIDS IHQLWKGTT QPMKLNTRPS TGLLRHILQQ VYNHSVTDPE KLNNYEPFSP EVYGETSFDL VAQMIDEIKM TDDDLFVDLG S GVGQVVLQ VAAATNCKHH YGVEKADIPA KYAETMDREF RKWMKWYGKK HAEYTLERGD FLSEEWRERI ANTSVIFVNN FA FGPEVDH QLKERFANMK EGGRIVSSKP FAPLNFRINS RNLSDIGTIM RVVELSPLKG SVSWTGKPVS YYLHTIDRTI LEN YFSSLK NP UniProtKB: Histone-lysine N-methyltransferase, H3 lysine-79 specific |
-Macromolecule #7: Ubiquitin
Macromolecule | Name: Ubiquitin / type: protein_or_peptide / ID: 7 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 8.576831 KDa |
Recombinant expression | Organism: Escherichia coli BL21 (bacteria) |
Sequence | String: MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKESTLHLV LRLRGG UniProtKB: Polyubiquitin-B |
-Macromolecule #8: S-ADENOSYLMETHIONINE
Macromolecule | Name: S-ADENOSYLMETHIONINE / type: ligand / ID: 8 / Number of copies: 1 / Formula: SAM |
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Molecular weight | Theoretical: 398.437 Da |
Chemical component information | ChemComp-SAM: |
-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 |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 37.28 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
+Image processing
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT |
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Output model | PDB-6jma: |