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Yorodumi- EMDB-4736: Structural basis of Cullin-2 RING E3 ligase regulation by the COP... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4736 | |||||||||
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Title | Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome | |||||||||
Map data | Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome | |||||||||
Sample |
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Keywords | Cullin-Ring E3 Ligase COP9 Signalosome Neddylation / LIGASE | |||||||||
Function / homology | Function and homology information 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 / regulation of cellular response to hypoxia / 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 / RHOBTB3 ATPase cycle / cullin-RING ubiquitin ligase complex / negative regulation of receptor signaling pathway via JAK-STAT / 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 / transcription elongation factor activity / 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) / Replication of the SARS-CoV-1 genome / 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 / intracellular non-membrane-bounded organelle / 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 / SUMOylation of ubiquitinylation proteins / Prolactin receptor signaling / negative regulation of transcription elongation by RNA polymerase II / skeletal muscle cell differentiation / protein monoubiquitination / 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 / ubiquitin-like ligase-substrate adaptor activity / response to light stimulus / 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 / negative regulation of signal transduction / regulation of cellular response to insulin stimulus / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / response to UV / JNK cascade / negative regulation of TORC1 signaling / 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 / negative regulation of autophagy / 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 / positive regulation of cell differentiation / 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 / 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 Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 8.4 Å | |||||||||
Authors | Morris EP / Faull SV | |||||||||
Funding support | United Kingdom, 1 items
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Citation | Journal: Nat Commun / Year: 2019 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 |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4736.map.gz | 38 MB | EMDB map data format | |
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Header (meta data) | emd-4736-v30.xml emd-4736.xml | 26.7 KB 26.7 KB | Display Display | EMDB header |
Images | emd_4736.png | 119.7 KB | ||
Filedesc metadata | emd-4736.cif.gz | 8.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4736 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4736 | HTTPS FTP |
-Validation report
Summary document | emd_4736_validation.pdf.gz | 364.9 KB | Display | EMDB validaton report |
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Full document | emd_4736_full_validation.pdf.gz | 364.5 KB | Display | |
Data in XML | emd_4736_validation.xml.gz | 6.8 KB | Display | |
Data in CIF | emd_4736_validation.cif.gz | 7.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4736 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4736 | HTTPS FTP |
-Related structure data
Related structure data | 6r6hMC 4739C 4741C 4742C 4744C 6r7fC 6r7hC 6r7iC 6r7nC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4736.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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
-Sample components
+Entire : Cullin-Ring E3 Ligases (CRLs) complexes with neddylated COP9 sign...
+Supramolecule #1: Cullin-Ring E3 Ligases (CRLs) complexes with neddylated COP9 sign...
+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 8
+Macromolecule #8: Cullin-2
+Macromolecule #9: Elongin-B
+Macromolecule #10: ELOC_HUMAN
+Macromolecule #11: RBX1_HUMAN
+Macromolecule #12: von Hippel-Lindau disease tumor suppressor
+Macromolecule #13: COP9 signalosome complex subunit 7b
+Macromolecule #14: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 Details: 15 mM Hepes pH 7.5 100 mM NaCl 0.5 mM DTT 1% glycerol |
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Vitrification | Cryogen name: NITROGEN / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 30 eV |
Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.8 µm / Nominal magnification: 47170 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 8.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 24040 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |