Abstract
To what extent do structural and biophysical features of food allergen proteins distinguish them from other proteins in our diet? Invertebrate tropomyosins (Tpms) as a class are considered "pan-allergens," inducing food allergy to shellfish and respiratory allergy to dust mites. Vertebrate Tpms are not known to elicit allergy or cross-reactivity, despite their high structural similarity and sequence identity to invertebrate homologs. We expect allergens are sufficiently stable against gastrointestinal proteases to survive for immune sensitization in the intestines, and that proteolytic stability will correlate with thermodynamic stability. Thermal denaturation of shrimp Tpm shows that it is more stable than non-allergen vertebrate Tpm. Shrimp Tpm is also more resistant to digestion. Molecular dynamics uncover local dynamics that select epitopes and global differences in flexibility between shrimp and pig Tpm that discriminate allergens from non-allergens. Molecular determinants of allergenicity depend not only on sequence but on contributions of protein structure and dynamics.