PXD042178

PXD042178 is an original dataset announced via ProteomeXchange.

Title	Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange
Description	Modular SCF (SKP1-CUL1-Fbox) ubiquitin E3 ligases orchestrate multiple cellular pathways in eukaryotes. Their variable SKP1-Fbox substrate receptor (SR) modules enable regulated substrate recruitment and subsequent proteasomal degradation. CAND proteins are essential for the efficient and timely exchange of SRs. To gain structural understanding of the underlying molecular mechanism, we reconstituted a CAND1-driven exchange reaction of substrate-bound SCF alongside its co-E3 ligase DCNL1 and visualised it by cryo-EM. We describe high-resolution structural intermediates including a ternary CAND1-SCF complex, as well as conformational and compositional intermediates representing SR- or CAND1-dissociation. We describe in molecular detail how CAND1-induced conformational changes in CUL1/RBX1 provide an optimised DCNL1 binding site and reveal an unexpected dual role for DCNL1 in CAND1-SCF dynamics. Moreover, a partially dissociated CAND1-SCF conformation accommodates cullin neddylation, leading to CAND1 displacement. Our structural findings, together with functional biochemical assays help formulate a detailed model for CAND-SCF regulation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:05:26.451.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Skehel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	SELECT SERIES Cyclic IMS

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-12 06:00:26	ID requested
1	2023-09-18 05:14:51	announced
⏵ 2	2023-11-14 09:05:34	announced	2023-11-14: Updated project metadata.

Shaaban M, Clapperton JA, Ding S, Kunzelmann S, M, ä, eots ME, Maslen SL, Skehel JM, Enchev RI, Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange. Mol Cell, 83(13):2332-2346.e8(2023) [pubmed]

submitter keyword: Human, CAND1, Cryo-EM, HDX-MS

Radoslav I. Enchev
contact affiliation	The Visual Biochemistry Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT London, UK.
contact email	radoslav.enchev@crick.ac.uk
lab head
Mark Skehel
contact affiliation	Francis Crick Institute
contact email	skehelm@crick.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/2023/09/PXD042178

PRIDE project URI

• PRIDE
  1. PXD042178
     1. Label: PRIDE project
     2. Name: Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange