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Yorodumi- PDB-9qo3: Dissociation-state-2 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: 9qo3 | ||||||||||||||||||||||||
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| Title | Dissociation-state-2 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex | ||||||||||||||||||||||||
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Keywords | LIGASE / COP9 signalosome / Cullin-RING E3 LIGASE | ||||||||||||||||||||||||
| 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 IRE1-mediated unfolded protein response / regulation of DNA damage response, signal transduction by p53 class mediator / 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 IRE1-mediated unfolded protein response / regulation of DNA damage response, signal transduction by p53 class mediator / 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 / PcG protein complex / COP9 signalosome / deubiquitinase activity / cullin-RING ubiquitin ligase complex / regulation of xenophagy / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / Cul7-RING ubiquitin ligase complex / cyclin-dependent protein serine/threonine kinase activator activity / regulation of cell cycle process / neural crest cell differentiation / protein neddylation / ubiquitin ligase activator activity / regulation of BMP signaling pathway / regulation of JNK cascade / regulation of mitophagy / Hydrolases; Acting on peptide bonds (peptidases) / regulation of centrosome duplication / RHOBTB1 GTPase cycle / metal-dependent deubiquitinase activity / regulation of TOR signaling / intercellular bridge / SCF ubiquitin ligase complex / regulation of DNA damage checkpoint / PRC1 complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Prolactin receptor signaling / ubiquitin ligase complex scaffold activity / response to light stimulus / limb development / positive regulation of keratinocyte differentiation / JNK cascade / cullin family protein binding / centrosome duplication / cilium assembly / cyclin-dependent protein kinase holoenzyme complex / ubiquitin-like ligase-substrate adaptor activity / positive regulation of double-strand break repair via homologous recombination / intrinsic apoptotic signaling pathway / ubiquitin ligase complex / protein K63-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / protein K48-linked ubiquitination / translation initiation factor activity / post-translational protein modification / molecular function activator activity / regulation of mitotic cell cycle / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / G1/S transition of mitotic cell cycle / ubiquitin binding / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Vpu mediated degradation of CD4 / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of CRY and PER proteins / Iron uptake and transport / Activation of NF-kappaB in B cells / Degradation of GLI1 by the proteasome / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / beta-catenin binding / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / GSK3B-mediated proteasomal degradation of PD-L1(CD274) / transcription by RNA polymerase II / NOTCH1 Intracellular Domain Regulates Transcription / regulation of circadian rhythm / Degradation of beta-catenin by the destruction complex / DNA Damage Recognition in GG-NER / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / metallopeptidase activity / FCERI mediated NF-kB activation / Formation of TC-NER Pre-Incision Complex / protein polyubiquitination / Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A / Interleukin-1 signaling / Orc1 removal from chromatin Similarity search - Function | ||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.6 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. | ||||||||||||||||||||||||
| History |
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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 | 9qo3.cif.gz | 663.4 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9qo3.ent.gz | 527.5 KB | Display | PDB format |
| PDBx/mmJSON format | 9qo3.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qo/9qo3 ftp://data.pdbj.org/pub/pdb/validation_reports/qo/9qo3 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 53255MC ![]() 9qo0C ![]() 9qo1C ![]() 9qo2C ![]() 9qo4C ![]() 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 ACDEFGHBP
| #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: 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: ![]() |
| #3: 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: ![]() |
| #4: Protein | Mass: 37621.742 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) |
| #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: ![]() |
| #12: 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: ![]() |
| #13: 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 , 2 types, 2 molecules IN
| #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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| #11: 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
| #9: 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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| #10: 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 




| #14: Chemical | ChemComp-ZN / |
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| #15: Chemical | ChemComp-IHP / |
| #16: 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 | 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: 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: 4.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 54098 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refinement | Highest resolution: 4.6 Å Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||
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About Yorodumi



Homo sapiens (human)
United Kingdom, 1items
Citation












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FIELD EMISSION GUN