Quantitative in silico evaluation of allergenic proteins from Anacardium occidentale, Carya illinoinensis, Juglans regia, and Pistacia vera and their epitopes as precursors of bioactive peptides

Authors: MINKIEWICZ, PIOTR - University Of Warmia; Mattison, Chris; DAREWICZ, MALGORZATA - University Of Warmia

Submitted to: Current Issues in Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/1/2022
Publication Date: 7/6/2022
Citation: Minkiewicz, P., Mattison, C.P., Darewicz, M. 2022. Quantitative in silico evaluation of allergenic proteins from Anacardium occidentale, Carya illinoinensis, Juglans regia, and Pistacia vera and their epitopes as precursors of bioactive peptides. Current Issues in Molecular Biology. 44(7): 3100-3117. https://doi.org/10.3390/cimb44070214.
DOI: https://doi.org/10.3390/cimb44070214

Interpretive Summary: The proteins we eat are digested by enzymes into smaller pieces called peptides. These peptides can sometimes contain biologically relevant activities in addition to their nutritional value. These “bioactivities” can be antimicrobial, antioxidative, or have other positive effects on bodily function, such as improving the immune system and vascular health among other things. It has been suggested that consumption of tree nuts has several health benefits, but tree nuts also contain proteins (allergens) that can also cause severe allergic reactions. Binding of human immunoglobulin E (IgE) antibodies to tree nut allergens leads to allergic symptoms that can sometimes be fatal. IgE binds to specific sequences on allergens called epitopes. We questioned if the allergen epitopes bound by IgE were more likely to also contain bioactivities when compared to allergen peptides that don’t bind IgE. Computer analysis of tree nut allergen protein sequences was used to identify potential bioactivities of peptides derived from tree nut allergens and determine if there was a correlation between IgE binding epitopes and bioactivities in the tree nut allergen peptides. However, in one type of tree nut allergen there was an increased amount of predicted bioactive peptides, but these peptides were not enriched in IgE binding. This study indicates that bioactive peptides in tree nut allergens are not enriched in IgE epitope sequences. The results indicate that there are factors other than peptide bioactivity that are responsible for these proteins acting as allergens.

Technical Abstract: Peptides derived from digested food proteins contain numerous types of potential bioactivities. Consumption of tree nuts is correlated to several health benefits and tree nuts contain many helpful bioactive compounds and peptides. However, seed storage proteins contained in tree nuts can also cause severe allergic reactions. The aim of the study presented here was to use in silico analysis to determine if there is a correlation between the presence of specific protein domains within tree nut allergens or tree nut allergen IgE epitopes and the frequency of bioactive peptides and predicted susceptibility to enzymatic digestion. The total frequency of bioactive peptide occurrence and the predicted total frequency of bioactive fragment release by the joint action of pepsin, trypsin, and chymotrypsin in proteins and IgE epitopes varies between families possessing different InterPro database domains. Proteins possessing a vicilin, N-terminal family domain, or napin domain contain a relatively low occurrence of bioactive fragments. In contrast, proteins possessing the cupin 1 domain without the vicilin N-terminal family domain contain a relatively high total frequency of bioactive fragments and predicted release of bioactive fragments by the joint action of pepsin, trypsin, and chymotrypsin. These bioactive peptides are distributed along the length of the protein and are not enriched in IgE epitope sequences.