PXD013001-1

PXD013001 is an original dataset announced via ProteomeXchange.

Title	HDX-MS of CSN-CRL2 complexes - Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome
Description	Cullin-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.
HostingRepository	PRIDE
AnnounceDate	2021-03-04
AnnouncementXML	Submission_2021-03-04_10:56:18.164.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andy Lau
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	SYNAPT G2-Si

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-06 07:34:41	ID requested
⏵ 1	2021-03-04 10:56:18	announced
2	2024-10-22 04:09:47	announced	2024-10-22: Updated project metadata.

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]

submitter keyword: Biological, conformational dynamics, protein-protein interactions, structural biology, COP9 signalosome, E3 Ligase

Argyris Politis
contact affiliation	King's College London, Chemistry Department, 7 Trinity Street, London, SE1 1DB, UK
contact email	argyris.politis@kcl.ac.uk
lab head
Andy Lau
contact affiliation	King's College London
contact email	andy.lau@kcl.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/09/PXD013001

PRIDE project URI

• PRIDE
  1. PXD013001
     1. Label: PRIDE project
     2. Name: HDX-MS of CSN-CRL2 complexes - Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome