PXD029655

PXD029655 is an original dataset announced via ProteomeXchange.

Title	Proteomic discovery of chemical probes that perturb protein complexes in human cells
Description	Most proteins in the human proteome lack chemical probes, and several large-scale and generalizable small-molecule binding assays have been introduced to address this problem. How compounds discovered in such “binding-first” assays affect protein function, nonetheless, often remains unclear. Here, we describe a “function-first” proteomic strategy that uses size exclusion chromatography (SEC) to assess the global impact of electrophilic compounds on protein complexes in human cells. Integrating the SEC data with cysteine-directed activity-based protein profiling identifies changes in protein-protein interactions that are caused by site-specific liganding events, including the stereoselective engagement of cysteines in PSME1 and SF3B1 that disrupt the PA28 proteasome regulatory complex and stabilize a dynamic state of the spliceosome, respectively. Our findings thus show how multidimensional proteomic analysis of focused libraries of electrophilic compounds can expedite the discovery of chemical probes with site-specific functional effects on protein complexes in human cells.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:58:51.940.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jarrett Remsberg
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-10 07:55:08	ID requested
1	2023-04-20 13:38:47	announced
⏵ 2	2023-11-14 08:58:52	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human, size-exclusion, chemoproteomics, immunopeptidomics, covalent ligands

Benjamin F. Cravatt
contact affiliation	Professor, Gilula Chair in Chemical Biology, The Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute 10550 North Torrey Pines Rd, La Jolla, CA 92037
contact email	cravatt@scripps.edu
lab head
Jarrett Remsberg
contact affiliation	Scripps Research Institute
contact email	remsberg@scripps.edu
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/PXD029655

PRIDE project URI

• PRIDE
  1. PXD029655
     1. Label: PRIDE project
     2. Name: Proteomic discovery of chemical probes that perturb protein complexes in human cells