PXD042178 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2023-09-18 |
AnnouncementXML | Submission_2023-09-18_05:14:50.326.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | MarkSkehel |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | SELECT SERIES Cyclic IMS |
Dataset History
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. |
Publication List
Shaaban M, Clapperton JA, Ding S, Kunzelmann S, M, รค, 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] |
Keyword List
submitter keyword: Human, CAND1, Cryo-EM, HDX-MS |
Contact List
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 | |
MarkSkehel |
contact affiliation | Francis Crick Institute |
contact email | skehelm@crick.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042178
- Label: PRIDE project
- Name: Structural and mechanistic insights into the CAND1-mediated SCF substrate receptor exchange