PXD027787

PXD027787 is an original dataset announced via ProteomeXchange.

Title	A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes
Description	Oxysterols (OHCs) are hydroxylated cholesterol metabolites that play ubiquitous roles in health and disease. Due to the non-covalent nature of their interactions and unique partitioning in membranes, the analysis of live-cell, proteome-wide interactions of OHCs remains an unmet challenge. In this Resource, we present a structurally precise chemoproteomics probe for the osteogenic molecule 20(S)-hydroxycholesterol (20(S)-OHC) and provide a map of its proteome-wide targets in the membranes of living cells. Our target catalogue consolidates diverse OHC ontologies and demonstrates that OHC-interacting proteins cluster with specific processes in immune response and cancer. Competition experiments reveal that 20(S)-OHC is a chemo-, regio-, and stereoselective ligand for the protein Tmem97 (σ2 receptor), enabling molecular reconstruction of the Tmem97:20(S)-OHC binding site. Our results demonstrate that multiplexed, quantitative analysis of cellular target engagement can expose new dimensions of OHC activity and identify actionable targets for molecular therapy.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:35:26.634.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brett Lomenick
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse; Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-06 03:45:45	ID requested
1	2021-11-29 06:19:06	announced
⏵ 2	2023-11-14 08:35:27	announced	2023-11-14: Updated project metadata.

Cheng YS, Zhang T, Ma X, Pratuangtham S, Zhang GC, Ondrus AA, Mafi A, Lomenick B, Jones JJ, Ondrus AE, A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes. Nat Chem Biol, 17(12):1271-1280(2021) [pubmed]

submitter keyword: Chemoproteomics Probe, Cancer,Oxysterols, Osteogenic Molecules, Immune Response, Live-cell Analysis

Alison E. Ondrus
contact affiliation	Caltech Division of Chemistry and Chemical Engineering
contact email	aondrus@caltech.edu
lab head
Brett Lomenick
contact affiliation	Caltech Proteome Exploration Lab
contact email	lomenick@caltech.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/2021/11/PXD027787

PRIDE project URI

• PRIDE
  1. PXD027787
     1. Label: PRIDE project
     2. Name: A proteome-wide map of 20(S)-hydroxycholesterol interactors in cell membranes