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- PDB-8ol1: cGAS-Nucleosome in complex with SPSB3-ELOBC (composite structure) -
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Open data
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Basic information
Entry | Database: PDB / ID: 8ol1 | ||||||
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Title | cGAS-Nucleosome in complex with SPSB3-ELOBC (composite structure) | ||||||
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![]() | IMMUNE SYSTEM / cGAS / degradation / UPS | ||||||
Function / homology | ![]() cyclic GMP-AMP synthase / 2',3'-cyclic GMP-AMP synthase activity / STING mediated induction of host immune responses / target-directed miRNA degradation / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / elongin complex / VCB complex / regulation of immunoglobulin production / cGAS/STING signaling pathway ...cyclic GMP-AMP synthase / 2',3'-cyclic GMP-AMP synthase activity / STING mediated induction of host immune responses / target-directed miRNA degradation / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / elongin complex / VCB complex / regulation of immunoglobulin production / cGAS/STING signaling pathway / Cul5-RING ubiquitin ligase complex / pattern recognition receptor signaling pathway / regulation of T cell activation / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / STAT family protein binding / cytoplasmic pattern recognition receptor signaling pathway / negative regulation of cGAS/STING signaling pathway / cGMP-mediated signaling / cellular response to exogenous dsRNA / ubiquitin-like protein ligase binding / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / positive regulation of type I interferon production / negative regulation of megakaryocyte differentiation / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / protein localization to CENP-A containing chromatin / negative regulation of double-strand break repair via homologous recombination / Formation of HIV elongation complex in the absence of HIV Tat / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / Packaging Of Telomere Ends / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / nucleosome binding / 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 / positive regulation of defense response to virus by host / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / RNA Polymerase II Pre-transcription Events / Inhibition of DNA recombination at telomere / Meiotic synapsis / phosphatidylinositol-4,5-bisphosphate binding / telomere organization / activation of innate immune response / RNA Polymerase I Promoter Opening / Interleukin-7 signaling / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / cAMP-mediated signaling / DNA methylation / Condensation of Prophase Chromosomes / transcription corepressor binding / 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 / molecular condensate scaffold activity / PRC2 methylates histones and DNA / Defective pyroptosis / transcription elongation by RNA polymerase II / HDACs deacetylate histones / determination of adult lifespan / RNA Polymerase I Promoter Escape / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Vif-mediated degradation of APOBEC3G / 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 / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Inactivation of CSF3 (G-CSF) signaling / B-WICH complex positively regulates rRNA expression / G2/M DNA damage checkpoint / HDMs demethylate histones / DNA Damage/Telomere Stress Induced Senescence / Evasion by RSV of host interferon responses / Metalloprotease DUBs / PKMTs methylate histone lysines / Meiotic recombination / RMTs methylate histone arginines / Regulation of expression of SLITs and ROBOs / 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 / UCH proteinases / positive regulation of cellular senescence / nucleosome / nucleosome assembly Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
![]() | Xu, P.B. / Ablasser, A. | ||||||
Funding support | European Union, 1items
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![]() | ![]() Title: The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation. Authors: Pengbiao Xu / Ying Liu / Chong Liu / Baptiste Guey / Lingyun Li / Pauline Melenec / Jonathan Ricci / Andrea Ablasser / ![]() ![]() Abstract: Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2'3'-cyclic GMP-AMP (cGAMP). ...Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2'3'-cyclic GMP-AMP (cGAMP). The indiscriminate activity of cGAS towards DNA demands tight regulatory mechanisms that are necessary to maintain cell and tissue homeostasis under normal conditions. Inside the cell nucleus, anchoring to nucleosomes and competition with chromatin architectural proteins jointly prohibit cGAS activation by genomic DNA. However, the fate of nuclear cGAS and its role in cell physiology remains unclear. Here we show that the ubiquitin proteasomal system (UPS) degrades nuclear cGAS in cycling cells. We identify SPSB3 as the cGAS-targeting substrate receptor that associates with the cullin-RING ubiquitin ligase 5 (CRL5) complex to ligate ubiquitin onto nuclear cGAS. A cryo-electron microscopy structure of nucleosome-bound cGAS in a complex with SPSB3 reveals a highly conserved Asn-Asn (NN) minimal degron motif at the C terminus of cGAS that directs SPSB3 recruitment, ubiquitylation and cGAS protein stability. Interference with SPSB3-regulated nuclear cGAS degradation primes cells for type I interferon signalling, conferring heightened protection against infection by DNA viruses. Our research defines protein degradation as a determinant of cGAS regulation in the nucleus and provides structural insights into an element of cGAS that is amenable to therapeutic exploitation. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 433.7 KB | Display | ![]() |
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PDB format | ![]() | 326.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 847.6 KB | Display | ![]() |
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Full document | ![]() | 927.5 KB | Display | |
Data in XML | ![]() | 52.2 KB | Display | |
Data in CIF | ![]() | 83.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 16936MC ![]() 8okxC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 6 types, 8 molecules AEBFKLMN
#1: Protein | Mass: 11546.513 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: H3C15, HIST2H3A, H3C14, H3F2, H3FM, HIST2H3C, H3C13, HIST2H3D Production host: ![]() ![]() #2: Protein | Mass: 9180.745 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, ...Gene: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, HIST1H4H, H4C9, H4/M, H4FM, HIST1H4I, H4C11, H4/E, H4FE, HIST1H4J, H4C12, H4/D, H4FD, HIST1H4K, H4C13, H4/K, H4FK, HIST1H4L, H4C14, H4/N, H4F2, H4FN, HIST2H4, HIST2H4A, H4C15, H4/O, H4FO, HIST2H4B, H4C16, H4-16, HIST4H4 Production host: ![]() ![]() #9: Protein | | Mass: 42202.590 Da / Num. of mol.: 1 / Mutation: K285A R300A K428A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #10: Protein | | Mass: 27415.240 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #11: Protein | | Mass: 12485.135 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #12: Protein | | Mass: 13147.781 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Histone H2A type 1- ... , 2 types, 2 molecules CG
#3: Protein | Mass: 11763.755 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#5: Protein | Mass: 11666.640 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Histone H2B type 1- ... , 2 types, 2 molecules DH
#4: Protein | Mass: 10623.174 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#6: Protein | Mass: 10493.994 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-DNA chain , 2 types, 2 molecules IJ
#7: DNA chain | Mass: 44552.379 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
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#8: DNA chain | Mass: 44961.633 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
-Non-polymers , 1 types, 1 molecules ![](data/chem/img/ZN.gif)
#13: Chemical | ChemComp-ZN / |
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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 |
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Sample preparation
Component | Name: cGAS-Spsb3-EloBC complex / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 / Details: PBS buffer |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 600 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20rc2_4400: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 592494 / Symmetry type: POINT | ||||||||||||||||||||||||
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