PXD071666

PXD071666 is an original dataset announced via ProteomeXchange.

Title	Thermal Proteome Prodiling and Glycoproteomics of U937 cells
Description	Protein glycosylation regulates essential cellular processes including protein folding, stability, and cell-cell interactions; however, how aberrant glycosylation impacts protein function and interaction networks remains poorly understood. Here we combine mass spectrometry-based proteomics, chemical glycobiology, and molecular dynamics simulations to systematically investigate glycosylation dependent protein stability and function. By perturbing the secretory pathway at defined steps, we generated proteins with distinct glycan structures and analyzed their functional consequences using thermal proteome profiling (TPP). This approach revealed that cells mount convergent stress responses to diverse glycosylation perturbations, characterized by coordinated trafficking reorganization. This reorganization effectively redirects protein flux from secretion toward degradation. We further identified that perturbing terminal glycan modifications, particularly sialylation and fucosylation, exerts the most profound effects on cell surface protein function. We studied in detail how loss of fucosylation restricts the conformational dynamics of key domains in integrin alpha 4, reducing VCAM-1 binding affinity and suggesting a potential therapeutic strategy for multiple sclerosis. Overall, our systematic approach uncovered extensive complexity in how glycosylation regulates protein function beyond simple glycoform identification and provides a resource for dissecting essential glycan-protein relationships.
HostingRepository	PRIDE
AnnounceDate	2025-12-11
AnnouncementXML	Submission_2025-12-11_00:04:15.129.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Johannes Hevler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-06 06:38:41	ID requested
⏵ 1	2025-12-11 00:04:15	announced

10.64898/2025.12.06.692499;

submitter keyword: Human monocytes with perturbed secretory pathway

Carolyn Bertozzi
contact affiliation	1Department of Chemistry and Sarafan Chem-H, Stanford University, Stanford, CA 94305, USA 2Howard Hughes Medical Institute, Stanford, CA 94305, USA
contact email	bertozzi@stanford.edu
lab head
Johannes Hevler
contact affiliation	Stanford University
contact email	hevlerjh@gmail.com
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/2025/12/PXD071666

PRIDE project URI

• PRIDE
  1. PXD071666
     1. Label: PRIDE project
     2. Name: Thermal Proteome Prodiling and Glycoproteomics of U937 cells