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PXD013001

PXD013001 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHDX-MS of CSN-CRL2 complexes - Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome
DescriptionCullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 (N8) from activated Cullins. The structure of stable CSN-CRL can be used to understand this mechanism of regulation. Here we present the first structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (MS). These structures reveal 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-MS we show that CRL2 binding and conformational activation of CSN5/CSN6 occur 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 identified novel sensory regions of the CSN that mediate its stepwise activation mechanism and provide a framework for better understanding the regulatory mechanism of other Cullin family members.
HostingRepositoryPRIDE
AnnounceDate2021-03-04
AnnouncementXMLSubmission_2021-03-04_10:56:18.164.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAndy Lau
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentSYNAPT G2-Si
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-03-06 07:34:41ID requested
12021-03-04 10:56:18announced
Publication List
Faull SV, Lau AMC, Martens C, Ahdash Z, Hansen K, Yebenes H, Schmidt C, Beuron F, Cronin NB, Morris EP, Politis A, Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome. Nat Commun, 10(1):3814(2019) [pubmed]
Keyword List
submitter keyword: Biological, conformational dynamics, protein-protein interactions, structural biology, COP9 signalosome, E3 Ligase
Contact List
Argyris Politis
contact affiliationKing's College London, Chemistry Department, 7 Trinity Street, London, SE1 1DB, UK
contact emailargyris.politis@kcl.ac.uk
lab head
Andy Lau
contact affiliationKing's College London
contact emailandy.lau@kcl.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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