Ole e 13 is the unique food allergen in olive: Structure-functional, substrates docking, and molecular allergenicity comparative analysis

Abstract

Thaumatin-like proteins (TLPs) are enzymes with important functions in pathogens defense and in the response to biotic and abiotic stresses. Last identified olive allergen (Ole e 13) is a TLP, which may also importantly contribute to food allergy and cross-allergenicity to pollen allergen proteins. The goals of this study are the characterization of the structural-functionality of Ole e 13 with a focus in its catalytic mechanism, and its molecular allergenicity by extensive analysis using different molecular computer-aided approaches covering a) functional-regulatory motifs, b) comparative study of linear sequence, 2-D and 3D structural homology modeling, c) molecular docking with two different β-D-glucans, d) conservational and evolutionary analysis, e) catalytic mechanism modeling, and f) IgE-binding, B- and T-cell epitopes identification and comparison to other allergenic TLPs. Sequence comparison, structure-based features, and phylogenetic analysis identified Ole e 13 as a thaumatin-like protein. 3D structural characterization revealed a conserved overall folding among plants TLPs, with mayor differences in the acidic (catalytic) cleft. Molecular docking analysis using two β-(1,3)-glucans allowed to identify fundamental residues involved in the endo-1,3-β-glucanase activity, and defining E84 as one of the conserved residues of the TLPs responsible of the nucleophilic attack to initiate the enzymatic reaction and D107 as proton donor, thus proposing a catalytic mechanism for Ole e 13. Identification of IgE-binding, B- and T-cell epitopes may help designing strategies to improve diagnosis and immunotherapy to food allergy and cross-allergenic pollen TLPs.

Keywords: Catalytic cleft; Electrostatic potential; Food allergy; Homology modeling; IgE-binding and T-cell epitopes; Molecular docking; Olea europaea L.; Osmotin; PR5 family.