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Yorodumi- PDB-9qo5: Dissociation-state-4 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: 9qo5 | ||||||||||||||||||||||||
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| Title | Dissociation-state-4 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 DNA damage response, signal transduction by p53 class mediator / 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 DNA damage response, signal transduction by p53 class mediator / regulation of IRE1-mediated unfolded protein response / Parkin-FBXW7-Cul1 ubiquitin ligase complex / exosomal secretion / GTPase inhibitor activity / deNEDDylase activity / activation of NF-kappaB-inducing kinase activity / synaptic assembly at neuromuscular junction / F-box domain binding / Aberrant regulation of mitotic exit in cancer due to RB1 defects / protein deneddylation / regulation of protein neddylation / eukaryotic translation initiation factor 3 complex / negative regulation of beige fat cell differentiation / PcG protein complex / COP9 signalosome / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / deubiquitinase activity / negative regulation of mitophagy / cullin-RING ubiquitin ligase complex / regulation of xenophagy / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / cellular response to chemical stress / Cul7-RING ubiquitin ligase complex / cyclin-dependent protein serine/threonine kinase activator activity / regulation of cell cycle process / neural crest cell differentiation / RNA polymerase II transcription initiation surveillance / positive regulation of protein autoubiquitination / protein neddylation / Hydrolases; Acting on peptide bonds (peptidases) / ubiquitin ligase activator activity / regulation of BMP signaling pathway / regulation of JNK cascade / NEDD8 ligase activity / regulation of mitophagy / RHOBTB1 GTPase cycle / negative regulation of response to oxidative stress / regulation of centrosome duplication / protein K27-linked ubiquitination / VCB complex / Cul5-RING ubiquitin ligase complex / metal-dependent deubiquitinase activity / regulation of TOR signaling / ubiquitin-ubiquitin ligase activity / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Cul2-RING ubiquitin ligase complex / SCF ubiquitin ligase complex / negative regulation of DNA-templated DNA replication / intercellular bridge / regulation of mitotic cytokinesis / Cul3-RING ubiquitin ligase complex / regulation of DNA damage checkpoint / negative regulation of type I interferon production / regulation of miRNA-mediated gene silencing / regulation of natural killer cell activation / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Prolactin receptor signaling / regulation of cell cycle phase transition / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / regulation of stem cell population maintenance / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of adipose tissue development / regulation of cellular response to stress / limb development / response to light stimulus / cyclin-dependent protein kinase holoenzyme complex / protein monoubiquitination / JNK cascade / cullin family protein binding / regulation of DNA-templated DNA replication initiation / centrosome duplication / protein K63-linked ubiquitination / cilium assembly / positive regulation of double-strand break repair via homologous recombination / ubiquitin-like ligase-substrate adaptor activity / intrinsic apoptotic signaling pathway / ribosome-associated ubiquitin-dependent protein catabolic process / signal transduction in response to DNA damage / negative regulation of insulin receptor signaling pathway / Nuclear events stimulated by ALK signaling in cancer / protein K48-linked ubiquitination / regulation of cellular response to insulin stimulus / positive regulation of TORC1 signaling / translation initiation factor activity / transcription-coupled nucleotide-excision repair / post-translational protein modification / cellular response to amino acid stimulus / regulation of embryonic development / replication fork processing / molecular function activator activity / negative regulation of canonical NF-kappaB signal transduction Similarity search - Function | ||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 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 | 9qo5.cif.gz | 680.5 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9qo5.ent.gz | 544.8 KB | Display | PDB format |
| PDBx/mmJSON format | 9qo5.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qo/9qo5 ftp://data.pdbj.org/pub/pdb/validation_reports/qo/9qo5 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 53257MC ![]() 9qo0C ![]() 9qo1C ![]() 9qo2C ![]() 9qo3C ![]() 9qo4C ![]() 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 ABCDFGHEP
| #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: 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: ![]() |
| #6: 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: ![]() |
| #7: 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: ![]() |
| #13: 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) |
| #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
| #8: 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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| #9: 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 |
| #12: 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
| #10: 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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| #11: 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, 3 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 | 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: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 500 nm / Nominal defocus min: 50 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: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 131512 / Symmetry type: POINT |
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Homo sapiens (human)
United Kingdom, 1items
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FIELD EMISSION GUN