Structural Characterization of the Allergenic 2S Albumin Cor a 14: Comparing Proteoform Patterns across Hazelnut Cultivars

Abstract

The hazelnut allergen Cor a 14 belongs to the 2S albumins, a family of heterodimeric seed storage proteins exhibiting a high degree of structural diversity. Given its relevance as an allergen and the potential to elicit severe reactions, elucidation of the sequence heterogeneity of naturally occurring Cor a 14 is essential for the development of reliable diagnostics and risk evaluation. We therefore performed a comprehensive survey on the proteoforms of Cor a 14 and determined their quantitative distribution in three different hazelnut cultivars by a combinatory HPLC-HRMS approach including bottom-up and intact mass analysis. Compared with the Cor a 14 prototype sequence, we identified three sequence polymorphisms, two of the small and one of the large subunit, and elucidated their specific pairing on the protein level. Furthermore, we located a pronounced microheterogeneity on the protein termini and, for the first time, provide data on varying proteoform patterns between different cultivars of an allergenic seed. Together, these data present the basis for a more detailed investigation on the allergenicity of Cor a 14 in different cultivars and constitute, to be best of our knowledge, the largest set of proteoforms so far reported for a 2S albumin.

Are Physicochemical Properties Shaping the Allergenic Potency of Plant Allergens?

“…In addition, minor clipping at the N-and C-terminal of both subunits provides extra variants (e.g. Cor a 14, hazelnut) [23,24]. Allergenic 2S albumins show a relatively low sequence identity among plant species, being more conserved among proteins from the same phylogenetic family [25].…”

Natural Variation of Hazelnut Allergenicity: Is There Any Potential for Selecting Hypoallergenic Varieties?

“…In fact, hazelnut is a wind-pollinated species and it has a self-incompatible mating system that enforces cross-pollination; thus, genetic diversity is expected to be high in naturally occurring plants [ 9 ]. The information on overall gene transcription patterns of hazelnut allergens is still very scarce [ 10 , 11 ] and their correlation with expressed proteins/allergens and its allergenic potential was not described. In this context, this project intends to investigate how natural inter-varietal genetic differences can affect the expression level of hazelnut allergens and their allergenic potential, aiming at selecting genotype candidates more suited for the consumer’s health, as the basis of promising desensitization strategies.…”

Effects of hazelnut protein isolate-induced food allergy on the gut microenvironment in a BALB/c mouse model

“…1A, mainly including Cor a 1, Cor a 8, Cor a 9, Cor a 11, and Cor a 14, which was also consistent with the previous studies. 25,26 The animal experimental protocol is shown in Fig. 1B.…”