PXD039649

PXD039649 is an original dataset announced via ProteomeXchange.

Title	Activity-based profiling of cullin-RING ligase networks by conformation-specific probes
Description	The cullin-RING E3 ligase (CRL) network comprises over 300 unique complexes that switch from inactive to activated conformations upon site-specific cullin modification by the ubiquitin-like protein NEDD8. Assessing cellular repertoires of activated CRL complexes is critical for understanding eukaryotic regulation. However, probes surveying networks controlled by site-specific ubiquitin-like protein modifications are lacking. We report development of a synthetic antibody recognizing the active conformation of a NEDD8-linked cullin. We established a pipeline probing cellular networks of activated CUL1-, CUL2-, CUL3- and CUL4-containing CRLs, revealing the CRL complexes responding to stimuli. Profiling several cell types showed their baseline neddylated CRL repertoires vary, prime efficiency of targeted protein degradation, and are differentially rewired across distinct primary cell activation pathways. Thus, conformation-specific probes can permit nonenzymatic activity-based profiling across a system of numerous multiprotein complexes, which in the case of neddylated CRLs reveals widespread regulation and could facilitate development of degrader drugs.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:03:01.784.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; 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	2023-01-25 03:36:12	ID requested
1	2023-09-11 04:21:22	announced
2	2023-11-14 09:05:10	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:03:02	announced	2024-10-22: Updated project metadata.

10.1038/s41589-023-01392-5;

Henneberg LT, Singh J, Duda DM, Baek K, Yanishevski D, Murray PJ, Mann M, Sidhu SS, Schulman BA, Activity-based profiling of cullin-RING E3 networks by conformation-specific probes. Nat Chem Biol, 19(12):1513-1523(2023) [pubmed]

submitter keyword: ligase,cullin, NEDD8, RING, ubiquitin, E3

Matthias Mann
contact affiliation	Dept. Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry
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/2023/09/PXD039649

PRIDE project URI

• PRIDE
  1. PXD039649
     1. Label: PRIDE project
     2. Name: Activity-based profiling of cullin-RING ligase networks by conformation-specific probes