+Open data
-Basic information
Entry | Database: PDB / ID: 8gui | |||||||||
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Title | Bre1-nucleosome complex (Model I) | |||||||||
Components |
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Keywords | GENE REGULATION/DNA / transcription / ubiquitin ligase / cancer / chromatin / GENE REGULATION / GENE REGULATION-DNA complex | |||||||||
Function / homology | Function and homology information histone H2B C-terminal K residue ubiquitin ligase activity / HULC complex / RHOBTB1 GTPase cycle / negative regulation of tumor necrosis factor-mediated signaling pathway / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / Packaging Of Telomere Ends ...histone H2B C-terminal K residue ubiquitin ligase activity / HULC complex / RHOBTB1 GTPase cycle / negative regulation of tumor necrosis factor-mediated signaling pathway / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / Packaging Of Telomere Ends / ubiquitin ligase complex / 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 / 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 / telomere organization / Meiotic synapsis / Interleukin-7 signaling / RNA Polymerase I Promoter Opening / epigenetic regulation of gene expression / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / DNA methylation / Regulation of endogenous retroelements by KRAB-ZFP proteins / Condensation of Prophase Chromosomes / HCMV Late Events / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / negative regulation of cell migration / innate immune response in mucosa / PRC2 methylates histones and DNA / Defective pyroptosis / mRNA 3'-UTR binding / HDACs deacetylate histones / RNA Polymerase I Promoter Escape / lipopolysaccharide binding / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RING-type E3 ubiquitin transferase / 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 / G2/M DNA damage checkpoint / HDMs demethylate histones / B-WICH complex positively regulates rRNA expression / DNA Damage/Telomere Stress Induced Senescence / heterochromatin formation / PKMTs methylate histone lysines / Metalloprotease DUBs / Meiotic recombination / Pre-NOTCH Transcription and Translation / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / Transcriptional regulation of granulopoiesis / protein polyubiquitination / ubiquitin-protein transferase activity / structural constituent of chromatin / UCH proteinases / ubiquitin protein ligase activity / antimicrobial humoral immune response mediated by antimicrobial peptide / nucleosome / p53 binding / nucleosome assembly / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / antibacterial humoral response / chromatin organization / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Factors involved in megakaryocyte development and platelet production / HATs acetylate histones / gene expression / Processing of DNA double-strand break ends / histone binding / Senescence-Associated Secretory Phenotype (SASP) / ubiquitin-dependent protein catabolic process / Oxidative Stress Induced Senescence / defense response to Gram-negative bacterium / Estrogen-dependent gene expression / killing of cells of another organism / chromosome, telomeric region / transcription coactivator activity / Ub-specific processing proteases / defense response to Gram-positive bacterium / protein ubiquitination / neuron projection / cadherin binding / protein heterodimerization activity / Amyloid fiber formation / ubiquitin protein ligase binding / chromatin binding / regulation of DNA-templated transcription / nucleolus Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.81 Å | |||||||||
Authors | Onishi, S. / Hamada, K. / Sato, K. / Nishizawa, T. / Nureki, O. / Ogata, K. / Sengoku, T. | |||||||||
Funding support | Japan, 1items
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Citation | Journal: Nat Commun / Year: 2024 Title: Structure of the human Bre1 complex bound to the nucleosome. Authors: Shuhei Onishi / Kotone Uchiyama / Ko Sato / Chikako Okada / Shunsuke Kobayashi / Keisuke Hamada / Tomohiro Nishizawa / Osamu Nureki / Kazuhiro Ogata / Toru Sengoku / Abstract: Histone H2B monoubiquitination (at Lys120 in humans) regulates transcription elongation and DNA repair. In humans, H2B monoubiquitination is catalyzed by the heterodimeric Bre1 complex composed of ...Histone H2B monoubiquitination (at Lys120 in humans) regulates transcription elongation and DNA repair. In humans, H2B monoubiquitination is catalyzed by the heterodimeric Bre1 complex composed of Bre1A/RNF20 and Bre1B/RNF40. The Bre1 proteins generally function as tumor suppressors, while in certain cancers, they facilitate cancer cell proliferation. To obtain structural insights of H2BK120 ubiquitination and its regulation, we report the cryo-electron microscopy structure of the human Bre1 complex bound to the nucleosome. The two RING domains of Bre1A and Bre1B recognize the acidic patch and the nucleosomal DNA phosphates around SHL 6.0-6.5, which are ideally located to recruit the E2 enzyme and ubiquitin for H2BK120-specific ubiquitination. Mutational experiments suggest that the two RING domains bind in two orientations and that ubiquitination occurs when Bre1A binds to the acidic patch. Our results provide insights into the H2BK120-specific ubiquitination by the Bre1 proteins and suggest that H2B monoubiquitination can be regulated by nuclesomal DNA flexibility. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8gui.cif.gz | 361.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8gui.ent.gz | 245.8 KB | Display | PDB format |
PDBx/mmJSON format | 8gui.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8gui_validation.pdf.gz | 906.5 KB | Display | wwPDB validaton report |
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Full document | 8gui_full_validation.pdf.gz | 919.4 KB | Display | |
Data in XML | 8gui_validation.xml.gz | 41 KB | Display | |
Data in CIF | 8gui_validation.cif.gz | 62.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gu/8gui ftp://data.pdbj.org/pub/pdb/validation_reports/gu/8gui | HTTPS FTP |
-Related structure data
Related structure data | 34274MC 8gujC 8gukC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 4 types, 8 molecules AEBFCGDH
#1: Protein | Mass: 15437.167 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) / References: UniProt: P68431 #2: Protein | Mass: 11263.231 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) / References: UniProt: P62805 #3: Protein | Mass: 13990.342 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) / References: UniProt: P0C0S8 #4: Protein | Mass: 14217.516 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: H2BC11, H2BFR, HIST1H2BJ / Production host: Escherichia coli (E. coli) / References: UniProt: P06899 |
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-DNA chain , 2 types, 2 molecules IJ
#5: DNA chain | Mass: 45145.754 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#6: DNA chain | Mass: 45604.047 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-E3 ubiquitin-protein ligase ... , 2 types, 2 molecules KL
#7: Protein | Mass: 113861.820 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RNF20, BRE1A / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q5VTR2, RING-type E3 ubiquitin transferase |
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#8: Protein | Mass: 113863.906 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RNF40, BRE1B, KIAA0661 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: O75150, RING-type E3 ubiquitin transferase |
-Non-polymers , 1 types, 4 molecules
#9: Chemical | ChemComp-ZN / |
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-Details
Has ligand of interest | N |
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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
Component |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 58 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 2.81 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 83000 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 68.02 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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