PXD038661

PXD038661 is an original dataset announced via ProteomeXchange.

Title	Systemwide disassembly and assembly of SCF ubiquitin ligase complexes
Description	Cells adapt to ever-changing environmental cues by remodeling their inventories of multiprotein complexes. The cellular repertoire of modular multiprotein SCF (SKP1-CUL1-Fbox protein) E3 ligase complexes - which mediate much protein degradation - requires CAND1 to distribute the limiting CUL1 subunit as needed across the family of ~70 different Fbox proteins. Yet how a single assembly factor coordinately promotes dissociation of idling complexes and formation of numerous distinct multiprotein complexes as needed remains unknown. Here, we address this by obtaining cryo-EM structures of CAND1-bound SCF complexes in multiple states, and correlating effects of mutations on the conformational ensembles and in biochemical and cellular assays. The data suggest CAND1 initially clasps catalytic domains of an inactive SCF, rolls around, and allosterically rocks and destabilizes the SCF interface. New SCF production proceeds in reverse, through SKP1 and the Fbox allosterically reducing interactions with CAND1. The CAND1-SCF conformational ensemble fuels mixing-and-matching of SCF parts in response to substrate availability. Thus, our data reveal the biogenesis of a predominant family of E3 ubiquitin ligases, and the molecular basis for systemwide multiprotein complex assembly.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:44:54.704.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-07 12:17:39	ID requested
1	2023-04-13 20:14:15	announced
⏵ 2	2023-11-14 08:45:07	announced	2023-11-14: Updated project metadata.

Baek K, Scott DC, Henneberg LT, King MT, Mann M, Schulman BA, Systemwide disassembly and assembly of SCF ubiquitin ligase complexes. Cell, 186(9):1895-1911.e21(2023) [pubmed]

submitter keyword: CRL, ligase, CAND1,SCF, formation, assembly, ubiquitin, complex, E3

Matthias Mann
contact affiliation	epartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
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/2023/04/PXD038661

PRIDE project URI

• PRIDE
  1. PXD038661
     1. Label: PRIDE project
     2. Name: Systemwide disassembly and assembly of SCF ubiquitin ligase complexes