dc.contributor.author | Faull, SV | |
dc.contributor.author | Lau, AMC | |
dc.contributor.author | Martens, C | |
dc.contributor.author | Ahdash, Z | |
dc.contributor.author | Hansen, K | |
dc.contributor.author | Yebenes, H | |
dc.contributor.author | Schmidt, C | |
dc.contributor.author | Beuron, F | |
dc.contributor.author | Cronin, NB | |
dc.contributor.author | Morris, EP | |
dc.contributor.author | Politis, A | |
dc.date.accessioned | 2019-09-19T09:08:23Z | |
dc.date.issued | 2019-08-23 | |
dc.identifier.citation | Nature communications, 2019, 10 (1), pp. 3814 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3354 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-019-11772-y | |
dc.description.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. 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. | |
dc.format | Electronic | |
dc.format.extent | 3814 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE RESEARCH | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Animals | |
dc.subject | Peptide Hydrolases | |
dc.subject | Ubiquitin-Protein Ligases | |
dc.subject | Intracellular Signaling Peptides and Proteins | |
dc.subject | Adaptor Proteins, Signal Transducing | |
dc.subject | Recombinant Proteins | |
dc.subject | Cryoelectron Microscopy | |
dc.subject | Protein Processing, Post-Translational | |
dc.subject | Mass Spectrometry | |
dc.subject | Sf9 Cells | |
dc.subject | COP9 Signalosome Complex | |
dc.subject | NEDD8 Protein | |
dc.title | Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-08-02 | |
rioxxterms.versionofrecord | 10.1038/s41467-019-11772-y | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-08-23 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Structural Electron Microscopy | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Structural Electron Microscopy | |
pubs.publication-status | Published | |
pubs.volume | 10 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Structural Electron Microscopy | |
dc.contributor.icrauthor | Beuron, Fabienne | |
dc.contributor.icrauthor | Morris, Edward | |