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PXD029655

PXD029655 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomic discovery of chemical probes that perturb protein complexes in human cells
DescriptionMost 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:58:51.940.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJarrett Remsberg
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-11-10 07:55:08ID requested
12023-04-20 13:38:47announced
22023-11-14 08:58:52announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Human, size-exclusion, chemoproteomics, immunopeptidomics, covalent ligands
Contact List
Benjamin F. Cravatt
contact affiliationProfessor, 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 emailcravatt@scripps.edu
lab head
Jarrett Remsberg
contact affiliationScripps Research Institute
contact emailremsberg@scripps.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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