PXD078458

PXD078458 is an original dataset announced via ProteomeXchange.

Title	Site-specific and Multiplexed Profiling of Bile Acid-Protein Interactions
Description	Bile acids (BAs) are a family of metabolites with an identical steroid core and versatile functional groups, which play central roles in digestion, metabolism and signaling. While endogenous receptors for selected BAs have been identified, a global BA-interactome map with site-specific resolution and ranked binding preferences is still lacking. Here, we report a high-throughput chemoproteomic platform named “SPIDER” that integrates ligand-directed release (LDR) chemistry with quantitative proteomics for site-specific and multiplexed profiling of BAs’ interactome. We applied SPIDER to quantify 770 interactions between six common BAs with 493 proteins in proteomes with both binding pockets mapped and binding preferences ranked. We discovered the microbiota-originated lithocholic acid (LCA) as an endogenous inhibitor of hydroxymethylglutaryl-CoA synthase 1 (HMGCS1), a key enzyme in the mevalonate pathway, and developed a potent covalent inhibitor for the enzyme based on an LCA-mimicking natural product to effectively lower nascent cholesterol biosynthesis. We further extended SPIDER to multiplexed interactome profiling of 19 FDA-approved drugs and established a comprehensive map of protein-drug interactions to guide drug screening and repurposing. These data highlight SPIDER as an enabling tool to streamline site-specific and comparative interactome profiling with diverse bioactive ligands in complex biological systems.
HostingRepository	iProX
AnnounceDate	2026-06-04
AnnouncementXML	Submission_2026-06-04_19:06:03.660.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yicheng Liu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	TMT6plex reporter+balance reagent acylated residue
Instrument	Orbitrap Eclipse; timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-18 00:14:08	ID requested
⏵ 1	2026-06-04 19:06:04	announced

Dataset with its publication pending

submitter keyword: Bile acid-protein interaction, Chemoproteomics, Drug-protein interaction

Chu Wang
contact affiliation	Peking University
contact email	chuwang@pku.edu.cn
lab head
Yicheng Liu
contact affiliation	Peking University
contact email	ycliu2055@outlook.com
dataset submitter

iProX dataset URI