Conclusions:
These results establish vicilin precursors as a family of evolutionarily distant, yet structurally similar proteins whose allergenic potential cannot be easily assessed using traditional sequence homology metrics. The cross-reactive peptides in the LSs are located in the most ordered region of the structures and are related in their PCPs to immunodominant epitopes of 2S-albumins. Concurrently, the widespread prevalence of what we refer to as repeat sequences, in a variety of common food sources, highlights the need for a combination of structural, bioinformatics and immunological tools to identify potential cross-reactivity between taxonomically distant allergen families. This emphasizes that while the α-hairpin structure is common and is likely to harbor important conformational epitopes, the location and sequence of the amino acids within the structure are likely to have a significant impact on the IgE binding affinity, the digestion sites, and the clinical relevance of IgE cross-reactivity.