PXD065689

PXD065689 is an original dataset announced via ProteomeXchange.

Title	Hydrogen-deuterium exchange mass spectrometry for molecular glue characterisation
Description	Molecular glues are powerful bioactive molecules that stabilize protein-protein interactions. Yet, the precise mechanisms by which many molecular glues exert their adhesive effects are still not well understood. Native mass spectrometry is an established technique used to monitor the stoichiometry and binding equilibria of molecular glue-induced protein-protein interactions. However, knowledge is lacking on how protein interaction dynamics change upon molecular glue-induced stabilization, and what conformational changes occur that enhance the stability of the resulting protein-protein-glue ternary complex. Here, we showcase hydrogen-deuterium exchange mass spectrometry (HDX-MS) as an analytical tool for molecular glue characterization. Using a broadly applicable molecular glue system involving the eukaryotic regulatory protein 14-3-3, its binding partners, and the molecular glue fusicoccin A, we show the power of HDX-MS in revealing not only molecular glue binding sites, but also conformational changes upon glue binding that result in differentially stabilized protein-protein complexes. Overall, we envisage our HDX-MS approach will become highly valuable for the characterization of molecular glues, guiding their optimization towards successful design.
HostingRepository	PRIDE
AnnounceDate	2025-07-30
AnnouncementXML	Submission_2025-07-30_04:27:20.660.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD065689
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Aneika Leney
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-02 08:15:02	ID requested
⏵ 1	2025-07-30 04:27:21	announced

10.6019/PXD065689;

10.1002/ADVS.202508543;

submitter keyword: Molecular glues, structural proteomics, native MS, protein-protein interactions, HDX-MS

Aneika C. Leney
contact affiliation	University of Birmingham
contact email	a.leney@bham.ac.uk
lab head
Aneika Leney
contact affiliation	University of Birmingham
contact email	a.leney@bham.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065689
     1. Label: PRIDE project
     2. Name: Hydrogen-deuterium exchange mass spectrometry for molecular glue characterisation