PXD056973

PXD056973 is an original dataset announced via ProteomeXchange.

Title	State-dependent ligandability profilling in human cells
Description	Post-translational modifications (PTMs) profoundly expand the diversity of the ~20,000 proteins encoded by the human genome and dynamically vary in response to changes in cellular environment, exposure to perturbagens, or the acquisition of disease. These changes can not only dramatically affect protein function, structure, and interactions but also the accessibility to small molecules (i.e. ligandability). Central to the development of "targeted therapies" are methods that not only identify proteins important for disease progression, but also enable the discovery of chemical probes that selectively engage these proteins under disease relevant conditions. In this study, we developed a chemoproteomic strategy to create global “fingerprints” that delineate alterations in protein ligandability in response to changes in PTM status. Employing fragment-based photoaffinity probes, we generated a comprehensive map of drug-like ligand-protein interactions that are sensitive to changes in N-glycosylation and phosphorylation in human cells. By integrating binding site information and structural analysis, we identified and orthogonally validated functionally diverse binding pockets whose ligandability is PTM-dependent. Among these targets, we discovered changes in the phosphorylation status of common oncogenic KRAS mutants affect accessibility to small molecules. Overall, our strategy unveils new insights into dynamic chemical tractability of the proteome mediated by PTMs and provides a blueprint for the development of chemical probes to selectively target proteins under specific states.
HostingRepository	PRIDE
AnnounceDate	2026-03-20
AnnouncementXML	Submission_2026-03-20_01:53:54.852.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weichao Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-19 14:47:35	ID requested
⏵ 1	2026-03-20 01:53:55	announced

Dataset with its publication pending

submitter keyword: glycosylation, state,PTM, phosphorylation

Christopher G. Parker
contact affiliation	Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA
contact email	cparker@scripps.edu
lab head
Weichao Li
contact affiliation	The Scripps Research Institute
contact email	wli@scripps.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/2026/03/PXD056973

PRIDE project URI

• PRIDE
  1. PXD056973
     1. Label: PRIDE project
     2. Name: State-dependent ligandability profilling in human cells