PXD065047

PXD065047 is an original dataset announced via ProteomeXchange.

Title	Mechanism of action of parasite TGFb antagonist via mouse (co-)receptors inspires creation of novel cell-type-specific TGFb modulators
Description	A murine parasite modulates host responses by secreting modular TGFβ mimics (TGMs). Among these, the agonist TGM1 consists of five distinct domains (D); D1/2, D3, and D4/5 interact with the host (co-)receptors TGFBR1, TGFBR2, and CD44, respectively. In contrast, antagonist TGM6 lacks the D1/2 domains that bind to TGFBR1 but retains thed3-TGFBR2 interaction. First, we found that TGM6 antagonize TGFb/SMAD signaling on mice but not on human cells, with the amino acid differences in the extracellular domain of TGFBR2 being responsible for this disparity. Next, we demonstrated that TGM6 competes with TGFβ for its interaction with mouse TGFBR. Importantly, we identified using biochemical assays that betaglycan and low-density lipoprotein receptor-related protein 1 (LRP1) act as TGM6 co-receptors. The D4/5 domains of TGM6 interact with LRP1, while betaglycan requires TGFBR2 for effective binding to TGM6-D3. Through genetic misexpression and cell biological experiments, we showed that LRP1 is essential for cell-specific antagonism by TGM6, while betaglycan counteracts TGM6's function. The modular structure of TGMs enabled us to create chimeras of TGM1 and TGM6, thereby changing TGM6 cell-type specificity and converting the antagonist into an agonist.
HostingRepository	PRIDE
AnnounceDate	2026-04-15
AnnouncementXML	Submission_2026-04-15_12:24:26.767.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Román González-Prieto
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-16 05:43:35	ID requested
⏵ 1	2026-04-15 12:24:27	announced

10.1002/ADVS.75322;

submitter keyword: Betaglycan/ Heminth polygyrus/ signal transduction/ transforming growth factor-b/ low density protein

Roman González-Prieto
contact affiliation	CABIMER - University of Sevilla
contact email	roman.gonzalez@cabimer.es
lab head
Román González-Prieto
contact affiliation	Andalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville
contact email	roman.gonzalez@cabimer.es
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/2026/04/PXD065047

PRIDE project URI

• PRIDE
  1. PXD065047
     1. Label: PRIDE project
     2. Name: Mechanism of action of parasite TGFb antagonist via mouse (co-)receptors inspires creation of novel cell-type-specific TGFb modulators