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- EMDB-33127: Cryo-EM structure of Dot1L and H2BK34ub-H3K79Nle nucleosome 2:1 c... -
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Open data
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Basic information
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Title | Cryo-EM structure of Dot1L and H2BK34ub-H3K79Nle nucleosome 2:1 complex | ||||||||||||||||||
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Function / homology | ![]() 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 / female meiosis I / regulation of receptor signaling pathway via JAK-STAT / 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 / female meiosis I / regulation of receptor signaling pathway via JAK-STAT / positive regulation of protein monoubiquitination / mitochondrion transport along microtubule / fat pad development / histone methyltransferase activity / female gonad development / seminiferous tubule development / male meiosis I / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Replacement of protamines by nucleosomes in the male pronucleus / heterochromatin formation / energy homeostasis / regulation of neuron apoptotic process / Packaging Of Telomere Ends / regulation of proteasomal protein catabolic process / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Maturation of protein E / Deposition of new CENPA-containing nucleosomes at the centromere / 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 / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / 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 / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / Inhibition of DNA recombination at telomere / Meiotic synapsis / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / telomere organization / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / RNA Polymerase I Promoter Opening / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / NRIF signals cell death from the nucleus / Regulation of PTEN localization / Assembly of the ORC complex at the origin of replication / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of BACH1 activity / Translesion synthesis by REV1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by POLK / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / DNA methylation / 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 / neuron projection morphogenesis / Regulation of activated PAK-2p34 by proteasome mediated degradation / Condensation of Prophase Chromosomes / 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 / 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 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / regulation of mitochondrial membrane potential / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / PRC2 methylates histones and DNA / Autodegradation of Cdh1 by Cdh1:APC/C / innate immune response in mucosa / TNFR1-induced NF-kappa-B signaling pathway / DNA damage checkpoint signaling / APC/C:Cdc20 mediated degradation of Securin Similarity search - Function | ||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.72 Å | ||||||||||||||||||
![]() | Ai HS / Liu AJ / Lou ZY / Liu L | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: H2B Lys34 Ubiquitination Induces Nucleosome Distortion to Stimulate Dot1L Activity. Authors: Huasong Ai / Maoshen Sun / Aijun Liu / Zixian Sun / Tingting Liu / Lin Cao / Lujun Liang / Qian Qu / Zichen Li / Zhiheng Deng / Zebin Tong / Guochao Chu / Xiaolin Tian / Haiteng Deng / Suwen ...Authors: Huasong Ai / Maoshen Sun / Aijun Liu / Zixian Sun / Tingting Liu / Lin Cao / Lujun Liang / Qian Qu / Zichen Li / Zhiheng Deng / Zebin Tong / Guochao Chu / Xiaolin Tian / Haiteng Deng / Suwen Zhao / Jia-Bin Li / Zhiyong Lou / Lei Liu / ![]() Abstract: Ubiquitination-dependent histone crosstalk plays critical roles in chromatin-associated processes and is highly associated with human diseases. Mechanism studies of the crosstalk have been of the ...Ubiquitination-dependent histone crosstalk plays critical roles in chromatin-associated processes and is highly associated with human diseases. Mechanism studies of the crosstalk have been of the central focus. Here our study on the crosstalk between H2BK34ub and Dot1L-catalyzed H3K79me suggests a novel mechanism of ubiquitination-induced nucleosome distortion to stimulate the activity of an enzyme. We determined the cryo-electron microscopy structures of Dot1L-H2BK34ub nucleosome complex and the H2BK34ub nucleosome alone. The structures reveal that H2BK34ub induces an almost identical orientation and binding pattern of Dot1L on nucleosome as H2BK120ub, which positions Dot1L for the productive conformation through direct ubiquitin-enzyme contacts. However, H2BK34-anchored ubiquitin does not directly interact with Dot1L as occurs in the case of H2BK120ub, but rather induces DNA and histone distortion around the modified site. Our findings establish the structural framework for understanding the H2BK34ub-H3K79me trans-crosstalk and highlight the diversity of mechanisms for histone ubiquitination to activate chromatin-modifying enzymes. | ||||||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.3 KB 23.3 KB | Display Display | ![]() |
Images | ![]() | 43.6 KB | ||
Others | ![]() ![]() | 59.6 MB 59.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 689.7 KB | Display | ![]() |
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Full document | ![]() | 689.3 KB | Display | |
Data in XML | ![]() | 11.3 KB | Display | |
Data in CIF | ![]() | 14.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7xctMC ![]() 7xcrC ![]() 7xd0C ![]() 7xd1C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_33127_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33127_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
+Entire : Complex of Dot1L(1-416) and H2BK34ub 2:1 nucleosome
+Supramolecule #1: Complex of Dot1L(1-416) and H2BK34ub 2:1 nucleosome
+Macromolecule #1: Ubiquitin
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A
+Macromolecule #4: Histone H2B type 1-K
+Macromolecule #5: Histone-lysine N-methyltransferase, H3 lysine-79 specific
+Macromolecule #6: Histone domain-containing protein
+Macromolecule #7: DNA (145-MER)
+Macromolecule #8: DNA (145-MER)
+Macromolecule #9: S-ADENOSYLMETHIONINE
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average exposure time: 2.56 sec. / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.72 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 98100 |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |