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Yorodumi- PDB-9qo4: Dissociation-state-3 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex -
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Open data
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Basic information
| Entry | Database: PDB / ID: 9qo4 | ||||||||||||||||||||||||
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| Title | Dissociation-state-3 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex | ||||||||||||||||||||||||
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Keywords | LIGASE / E3 ligases / COP9 signalosome | ||||||||||||||||||||||||
| Function / homology | Function and homology informationnegative regulation of protein localization to nucleolus / negative regulation of protein neddylation / COP9 signalosome assembly / macrophage migration inhibitory factor binding / regulation of xenophagy / regulation of IRE1-mediated unfolded protein response / Parkin-FBXW7-Cul1 ubiquitin ligase complex / exosomal secretion / GTPase inhibitor activity / deNEDDylase activity ...negative regulation of protein localization to nucleolus / negative regulation of protein neddylation / COP9 signalosome assembly / macrophage migration inhibitory factor binding / regulation of xenophagy / regulation of IRE1-mediated unfolded protein response / Parkin-FBXW7-Cul1 ubiquitin ligase complex / exosomal secretion / GTPase inhibitor activity / deNEDDylase activity / F-box domain binding / synaptic assembly at neuromuscular junction / Aberrant regulation of mitotic exit in cancer due to RB1 defects / activation of NF-kappaB-inducing kinase activity / protein deneddylation / regulation of cell cycle process / neural crest cell differentiation / regulation of protein neddylation / eukaryotic translation initiation factor 3 complex / regulation of BMP signaling pathway / PcG protein complex / negative regulation of beige fat cell differentiation / regulation of mitophagy / COP9 signalosome / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / deubiquitinase activity / regulation of centrosome duplication / cullin-RING ubiquitin ligase complex / maintenance of protein location in nucleus / Cul7-RING ubiquitin ligase complex / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / cellular response to chemical stress / cyclin-dependent protein serine/threonine kinase activator activity / regulation of TOR signaling / positive regulation of protein autoubiquitination / RNA polymerase II transcription initiation surveillance / protein neddylation / ubiquitin ligase activator activity / regulation of DNA damage checkpoint / Hydrolases; Acting on peptide bonds (peptidases) / NEDD8 ligase activity / regulation of JNK cascade / regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of response to oxidative stress / RHOBTB1 GTPase cycle / protein K27-linked ubiquitination / VCB complex / Cul5-RING ubiquitin ligase complex / metal-dependent deubiquitinase activity / ubiquitin-ubiquitin ligase activity / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / Cul3-RING ubiquitin ligase complex / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / intercellular bridge / negative regulation of mitophagy / Prolactin receptor signaling / limb development / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / centrosome duplication / response to light stimulus / cilium assembly / JNK cascade / protein monoubiquitination / cullin family protein binding / protein K63-linked ubiquitination / cyclin-dependent protein kinase holoenzyme complex / positive regulation of double-strand break repair via homologous recombination / GSK3B-mediated proteasomal degradation of PD-L1(CD274) / ubiquitin-like ligase-substrate adaptor activity / signal transduction in response to DNA damage / site of DNA damage / Nuclear events stimulated by ALK signaling in cancer / protein K48-linked ubiquitination / negative regulation of insulin receptor signaling pathway / regulation of cellular response to insulin stimulus / positive regulation of TORC1 signaling / translation initiation factor activity / animal organ morphogenesis / transcription-coupled nucleotide-excision repair / intrinsic apoptotic signaling pathway / post-translational protein modification / regulation of mitotic cell cycle / molecular function activator activity / negative regulation of canonical NF-kappaB signal transduction / cellular response to amino acid stimulus / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / T cell activation / ubiquitin binding / G1/S transition of mitotic cell cycle / negative regulation of canonical Wnt signaling pathway / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling Similarity search - Function | ||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.95 Å | ||||||||||||||||||||||||
Authors | Ding, S. / Clapperton, J.A. / Maeots, M.E. / Enchev, R.I. | ||||||||||||||||||||||||
| Funding support | United Kingdom, 1items
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Citation | Journal: Nat Commun / Year: 2026Title: Structural basis of CSN-mediated SCF deneddylation. Authors: Shan Ding / Julie A Clapperton / Märt-Erik Mäeots / Simone Kunzelmann / Mohammed Shaaban / Radoslav I Enchev / ![]() Abstract: Cullin-RING ligases (CRLs) are the largest family of E3 ligases, with ubiquitination activity dynamically regulated by neddylation and deneddylation by the COP9 signalosome (CSN). CSN-mediated ...Cullin-RING ligases (CRLs) are the largest family of E3 ligases, with ubiquitination activity dynamically regulated by neddylation and deneddylation by the COP9 signalosome (CSN). CSN-mediated deneddylation not only deactivates CRLs but also enables substrate receptor exchange. Although CSN is a promising drug target, the structural basis underlying its catalytic mechanism remains unclear. Here, we use cryo-electron microscopy (cryo-EM) to uncover distinct functional states of CSN-CRL (SCF) complexes, capturing key intermediates of the deneddylation cycle. We visualise an autoinhibited docking state and a catalytic intermediate in which CSN5 Ins-1 loop, RBX1 RING and neddylated Cullin WHB domains are repositioned for isopeptide cleavage. We further resolve four dissociation intermediates that define the stepwise release of CSN from its product, with RBX1 RING stabilising key interactions. Additionally, our structures locate CSNAP within a CSN3-CSN8 groove. Together, our study provides a mechanistic model for CSN function and informs the rational design of CSN-targeted therapeutics. | ||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9qo4.cif.gz | 772 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9qo4.ent.gz | 619 KB | Display | PDB format |
| PDBx/mmJSON format | 9qo4.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qo/9qo4 ftp://data.pdbj.org/pub/pdb/validation_reports/qo/9qo4 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 53256MC ![]() 9qo0C ![]() 9qo1C ![]() 9qo2C ![]() 9qo3C ![]() 9qo5C ![]() 9qo6C M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-COP9 signalosome complex subunit ... , 9 types, 9 molecules ABCDEFGHP
| #1: Protein | Mass: 55606.496 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GPS1, COPS1, CSN1 / Production host: ![]() |
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| #2: Protein | Mass: 51664.570 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COPS2, CSN2, TRIP15 / Production host: ![]() |
| #3: Protein | Mass: 47924.008 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COPS3, CSN3 / Production host: ![]() |
| #4: Protein | Mass: 46322.688 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COPS4, CSN4 / Production host: ![]() |
| #5: Protein | Mass: 37563.707 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COPS5, CSN5, JAB1 / Production host: ![]() References: UniProt: Q92905, Hydrolases; Acting on peptide bonds (peptidases) |
| #6: Protein | Mass: 36203.398 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COPS6, CSN6, HVIP / Production host: ![]() |
| #7: Protein | Mass: 29656.928 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COPS7B, CSN7B / Production host: ![]() |
| #8: Protein | Mass: 23245.543 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COPS8, CSN8 / Production host: ![]() |
| #14: Protein | Mass: 6213.689 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: COPS9, MYEOV2 / Production host: ![]() |
-Protein , 3 types, 3 molecules IJN
| #9: Protein | Mass: 89800.367 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CUL1 / Production host: ![]() |
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| #10: Protein | Mass: 12289.977 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RBX1, RNF75, ROC1 / Production host: ![]() References: UniProt: P62877, RING-type E3 ubiquitin transferase, cullin-RING-type E3 NEDD8 transferase |
| #13: Protein | Mass: 9679.211 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CKS1B, CKS1, PNAS-143, PNAS-16 / Production host: ![]() |
-S-phase kinase-associated protein ... , 2 types, 2 molecules LM
| #11: Protein | Mass: 18679.965 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SKP1, EMC19, OCP2, SKP1A, TCEB1L / Production host: ![]() |
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| #12: Protein | Mass: 47817.785 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SKP2, FBXL1 / Production host: ![]() |
-Non-polymers , 3 types, 6 molecules 




| #15: Chemical | ChemComp-IHP / | ||
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| #16: Chemical | ChemComp-ZN / #17: Water | ChemComp-HOH / | |
-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-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
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| Buffer solution | pH: 7.5 / Details: 15 mM Hepes pH 7.5, 120 mM NaCl, 0.5 mM DTT | ||||||||||||||||||||||||||||||||||||
| Specimen | Conc.: 3.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 5000 nm / Nominal defocus min: 500 nm |
| Image recording | Electron dose: 47 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||
| 3D reconstruction | Resolution: 2.95 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 409455 / Symmetry type: POINT |
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About Yorodumi



Homo sapiens (human)
United Kingdom, 1items
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FIELD EMISSION GUN