Structural Bases for the Allergenicity of Fra a 1.02 in Strawberry Fruits

Abstract

Although strawberries are highly appreciated fruits, their intake can induce allergic reactions in atopic patients. These reactions can be due to the patient's previous sensitization to the major birch pollen allergen Bet v 1, by which IgE generated in response to Bet v 1 cross-reacts with the structurally related strawberry Fra a 1 protein family. Fra a 1.02 is the most expressed paralog in ripe strawberries and is highly allergenic. To better understand the molecular mechanisms regulating this allergic response, we have determined the three-dimensional structure of Fra a 1.02 and four site-directed mutants that were designed based on their positions in potential epitopes. Fra a 1.02 and mutants conform to the START fold. We show that the cross-reactivity of all the mutant variants to IgE from patients allergic to Bet v 1 was significantly reduced without altering the conserved structural fold, so that they could potentially be used as hypoallergenic Fra a 1 variants for the generation of vaccines against strawberry allergy in atopic patients. Article pubs.acs.org/JAFC Cite This: J. Agric. Food Chem. XXXX, XXX, XXX−XXX

PR10/Bet v1‐like Proteins as Novel Contributors to Plant Biochemical Diversity

“…The conserved glycine-rich loop corresponds to L3, which links β2 and β3 (Figure 7a). These secondary structure elements and their arrangements are highly conserved among closely-related Bet v1 homologues in other species such as peanut (Ara h 8 [112] ), apple (Mal d 1 [113] ), hazelnut (Cor a 1.0401 [114] ), and strawberry (Fra a 1 variants [115] ) and among the other dicot PR10s including LlPR-10 [74,116] and Hyp-1 [29] (Figure 7b).…”

“…Fra a 2 myricetin ITC [61] Fra a 3 (+)-catechin co-crystallization and ITC [61] Fra a 1.02 myricetin docking simulation [115] LlPR-10.1A trans-zeatin co-crystallization and circular dichroism spectroscopy [74] LlPR-10.2B zeatin co-crystallization [28] N,N'-diphenylurea co-crystallization and ITC [127] melatonin co-crystallization [42] VrPhBP zeatin and N-(2-chloro-4-pyridyl)-N'phenylurea co-crystallization, fluorescence assay, and/or ITC [27] cytokinins (zeatin, 6-(γ,γ-dimethylallyl-amino) purine), synthetic cytokinins (4-PU, 4-CPPU), and gibberellins (GA3, GA4 and GA9 methyl ester) fluorescence assay [123] gibberellic acid and trans-zeatin (weaker affinity) co-crystallization and ITC [31] MtPhBP gibberellic acid and trans-zeatin (weaker affinity)…”

Down-regulation of Fra a 1.02 in strawberry fruits causes transcriptomic and metabolic changes compatible with an altered defense response

“…This cavity also presents some polar residues that facilitate the binding of small ligands 1 . Several crystal structures of Fra a 1.01E, Fra a 1.02 and Fra a 1.03, the last one bound to catechin, have been resolved 11,12 . These structures show high similarity, and they all exhibit the characteristic START fold.…”

“…In addition, a flavonoid glycoside has been identified as natural ligand of Mal d 1, a homologous protein to Fra a 1 from apple 13 . The functional relevance of these interactions remains unclear, but the specificity of the interactions and the subtle conformational change associated to the natural ligand binding 11,12 suggest that Fra a 1 proteins could play a regulatory role in intracellular signaling.…”

Structural basis for variable IgE reactivities of Cor a 1 hazelnut allergens

“…This amphiphilic area extends to an entrance of the cavity (ε1), which is located between helix α3 and strands β3 and β4, as well as loops L5 and L6. The amphiphilic nature of the cavity has also been reported for other food and pollen allergens (Ahammer, Grutsch, Kamenik, Liedl, & Tollinger, 2017; Kofler et al, 2012; Orozco-Navarrete et al, 2020). Of note, the exact composition of the internal cavity in the four Cor a 1.04 isoforms is fairly diverse, in particular regarding the contributions from hydrophobic and charged residues (Figure 2 C).…”