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- EMDB-4742: Structural basis of Cullin-2 RING E3 ligase regulation by the COP... -
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Basic information
Entry | Database: EMDB / ID: EMD-4742 | |||||||||
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Title | Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome | |||||||||
![]() | Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome | |||||||||
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Function / homology | ![]() nucleotide-excision repair factor 4 complex / regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / regulation of IRE1-mediated unfolded protein response / global genome nucleotide-excision repair / exosomal secretion / deNEDDylase activity / GTPase inhibitor activity ...nucleotide-excision repair factor 4 complex / regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / regulation of IRE1-mediated unfolded protein response / global genome nucleotide-excision repair / exosomal secretion / deNEDDylase activity / GTPase inhibitor activity / regulation of protein neddylation / protein deneddylation / eukaryotic translation initiation factor 3 complex / activation of NF-kappaB-inducing kinase activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / COP9 signalosome / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / regulation of proteolysis / target-directed miRNA degradation / elongin complex / VCB complex / positive regulation of protein autoubiquitination / protein neddylation / regulation of JNK cascade / metal-dependent deubiquitinase activity / Hydrolases; Acting on peptide bonds (peptidases) / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / RHOBTB1 GTPase cycle / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / inner cell mass cell proliferation / Cul2-RING ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / TP53 Regulates Transcription of DNA Repair Genes / Prolactin receptor signaling / skeletal muscle cell differentiation / protein monoubiquitination / TGF-beta receptor signaling activates SMADs / cullin family protein binding / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / Antigen processing: Ubiquitination & Proteasome degradation / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / response to light stimulus / anatomical structure morphogenesis / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / protein K48-linked ubiquitination / Formation of HIV elongation complex in the absence of HIV Tat / post-translational protein modification / Nuclear events stimulated by ALK signaling in cancer / regulation of cellular response to insulin stimulus / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / response to UV / JNK cascade / RNA Polymerase II Pre-transcription Events / positive regulation of TORC1 signaling / T cell activation / translation initiation factor activity / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / cellular response to amino acid stimulus / transcription corepressor binding / Degradation of DVL / nucleotide-excision repair / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / transcription elongation by RNA polymerase II / Negative regulation of NOTCH4 signaling / Iron uptake and transport / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / positive regulation of DNA-binding transcription factor activity / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / Orc1 removal from chromatin / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / DNA Damage Recognition in GG-NER / protein modification process / RING-type E3 ubiquitin transferase / negative regulation of canonical Wnt signaling pathway / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.9 Å | |||||||||
![]() | Faull SF / Lau AMC / Beuron F / Cronin NB / Morris EP / Politis A | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome. Authors: Sarah V Faull / Andy M C Lau / Chloe Martens / Zainab Ahdash / Kjetil Hansen / Hugo Yebenes / Carla Schmidt / Fabienne Beuron / Nora B Cronin / Edward P Morris / Argyris Politis / ![]() ![]() ![]() Abstract: Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. ...Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Using hydrogen-deuterium exchange (HDX)-MS we show that CRL2 activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Overall, by synergising cryo-EM with MS, we identify sensory regions of the CSN that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 37.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 27.4 KB 27.4 KB | Display Display | ![]() |
Images | ![]() | 131.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6r7iMC ![]() 4736C ![]() 4739C ![]() 4741C ![]() 4744C ![]() 6r6hC ![]() 6r7fC ![]() 6r7hC ![]() 6r7nC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : CSN-CRL2-N8
+Supramolecule #1: CSN-CRL2-N8
+Macromolecule #1: COP9 signalosome complex subunit 1
+Macromolecule #2: COP9 signalosome complex subunit 2
+Macromolecule #3: COP9 signalosome complex subunit 3
+Macromolecule #4: COP9 signalosome complex subunit 4
+Macromolecule #5: COP9 signalosome complex subunit 5
+Macromolecule #6: COP9 signalosome complex subunit 6
+Macromolecule #7: COP9 signalosome complex subunit 7b
+Macromolecule #8: COP9 signalosome complex subunit 8
+Macromolecule #9: NEDD8
+Macromolecule #10: Cullin-2
+Macromolecule #11: Elongin-B
+Macromolecule #12: Elongin-C
+Macromolecule #13: E3 ubiquitin-protein ligase RBX1
+Macromolecule #14: ZINC ION
+Macromolecule #15: water
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 5.0 nm / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 2 / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 75.0 µm / Calibrated defocus max: 3.0 µm / Calibrated defocus min: 1.8 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
CTF correction | Software - Name: RELION |
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Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 5.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 316921 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |