The Celiac-Disease Superantigen Oligomerizes and Increases Permeability in an Enterocyte Cell Model

Angew Chem Int Ed Engl. 2024 Mar 18:e202317552. doi: 10.1002/anie.202317552. Online ahead of print.ABSTRACTCeliac disease (CeD) is an autoimmune disorder triggered by gluten proteins, affecting approximately 1% of the global population. The 33-mer deamidated gliadin peptide (DGP) is a metabolically modified wheat-gluten superantigen for CeD. Here, we demonstrate that the 33-mer DGP spontaneously assembles into oligomers with a diameter of approximately 24 nm. The 33-mer DGP oligomers present two main secondary structural motifs-a major polyproline II helix and a minor β-sheet structure. Importantly, in the presence of 33-mer DGP oligomers, there is a statistically significant increase in the permeability in the gut epithelial cell model Caco-2, accompanied by the redistribution of zonula occludens-1, a master tight junction protein. These findings provide novel molecular and supramolecular insights into the impact of 33-mer DGP in CeD and highlight the relevance of gliadin peptide oligomerization.PMID:38497459 | DOI:10.1002/anie.202317552
Source: Angewandte Chemie - Category: Chemistry Authors: Source Type: research