PXD068828-1

PXD068828 is an original dataset announced via ProteomeXchange.

Title	Membrane mimetic thermal proteome profiling (MM-TPP) towards mapping membrane protein-ligand dynamic interactions
Description	Integral membrane proteins (IMPs) are key targets for small-molecule therapeutics. However, robust, unbiased, and detergent-free methods to probe on- and off-target interactions within this protein class remain underdeveloped. Previously, we introduced the Peptidisc membrane mimetic (MM) for water-soluble stabilization of the membrane proteome and interactome (Carlson et al., 2019). Here, we integrate the Peptidisc with thermal proteome profiling (TPP) to establish membrane mimetic thermal proteome profiling (MM-TPP), a method that enables proteome-wide characterization of membrane protein–ligand interactions. Using a membrane protein library derived from the mouse liver, we assessed the specific effects of ATP and orthovanadate on the thermal stability of ATP-binding cassette (ABC) transporters, but also stability shifts driven by the hydrotropic effect of ATP and its by-products on G protein–coupled receptors (GPCRs). Conversely, when tested in detergent-based TPP (DB-TPP) using ATP–VO₄, no specific enrichment of ATP-binding protein were obtained, highlighting the utility of MM-TPP. As an additional validation step, we tested MM-TPP’s ability to capture specific ligand-induced stabilization of cognate targets, here demonstrated by the selective thermal stabilization of the P2RY12 receptor by 2-methylthio-ADP. Altogether, MM-TPP emerges as a robust platform for identifying both on- and off-target effects of small molecules, offering new insights into the druggable membrane proteome and its stability landscape as a consequence of changing and often dynamic small molecules.
HostingRepository	PRIDE
AnnounceDate	2025-11-17
AnnouncementXML	Submission_2025-11-16_17:34:12.483.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ashim Bhattacharya
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-25 04:36:58	ID requested
⏵ 1	2025-11-16 17:34:13	announced

Jandu RS, Bhattacharya A, Antony F, Al-Seragi M, Aoki H, Babu M, Duong van Hoa F, Membrane-mimetic thermal proteome profiling (MM-TPP) toward mapping membrane protein-ligand dynamic interactions. Elife, 14():(2025) [pubmed]

10.7554/elife.104549;

submitter keyword: Membrane Proteins, orbitrap exploris, mus musculus, Membrane Mimetic Thermal Proteome Profiling, Proteomics

Franck Duong
contact affiliation	University of British Columbia, Faculty of Medicine, Department of Biochemistry and Molecular Biology, Life Sciences Institute
contact email	fduong@mail.ubc.ca
lab head
Ashim Bhattacharya
contact affiliation	University of British Columbia
contact email	ashim938@student.ubc.ca
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/2025/11/PXD068828

PRIDE project URI

• PRIDE
  1. PXD068828
     1. Label: PRIDE project
     2. Name: Membrane mimetic thermal proteome profiling (MM-TPP) towards mapping membrane protein-ligand dynamic interactions