Thin‐Plate Superstructures of the Immunogenic 33‐mer Gliadin Peptide

Gluten related‐disorders have a prevalence of 1–5 % worldwide triggered by the ingestion of gluten proteins in wheat, rye, barley, and some oats. In wheat gluten, the most studied protein is gliadin, whose immunodominant 33‐mer amino acid fragment remains after digestive proteolysis and accumulates in the gut mucosa. Here, we report the formation of 33‐mer thin‐plate superstructures using intrinsic tyrosine (Tyr) steady‐state fluorescence anisotropy and cryo‐TEM in combination with water tension measurements. Furthermore, we showed that fluorescence decay measurements of 33‐mer intrinsic fluorophore Tyr provided information on the early stages of the formation of the thin‐plate structures. Finally, conformational analysis of Tyr residues using minimalist models by molecular dynamic simulations (MD) demonstrated that changes in Tyr rotamer states depend on the oligomerization stage. Our findings further advance the understanding of the formation of the 33‐mer gliadin peptide superstructures and their relation to health and disease. The immunogenic 33‐mer gliadin peptide builds up thin‐plate superstructures that could be responsible for an innate immune response in the context of gluten‐related disorders. A multi‐technique evaluation provides insight into the self‐assembly process showing that the intrinsic tyrosine fluorescence is a sensor for monitoring the formation of the thin‐plate structures.