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bioRxiv · 10.1101/2020.11.27.400978

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

Fuehrer, S.·Kamenik, A. S.·Zeindl, R.·Nothegger, B.·Hofer, F.·Reider, N.·Liedl, K. R.·Tollinger, M.
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Abstract

A major proportion of allergic reactions to hazelnuts (Corylus avellana) are caused by immunologic cross-reactivity of IgE antibodies to pathogenesis-related class 10 (PR-10) proteins. Intriguingly, the four known isoforms of the hazelnut PR-10 allergen Cor a 1, denoted as Cor a 1.0401-Cor a 1.0404, share sequence identities exceeding 97 % but possess different immunologic properties. In this work we describe the NMR solution structures of these proteins and provide an in-depth study of their biophysical properties. Despite sharing highly similar three-dimensional structures, the four isoforms exhibit remarkable differences regarding structural flexibility, hydrogen bonding and thermal stability. Our experimental data reveal an inverse correlation between structural flexibility and IgE-binding, with the most flexible isoform having the lowest IgE-binding potential, while the isoform with the most rigid backbone scaffold displays the highest immunologic reactivity. These results point towards a significant entropic contribution to the process of antibody binding.

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Fuehrer, S., Kamenik, A. S., Zeindl, R., Nothegger, B., Hofer, F., Reider, N., Liedl, K. R., Tollinger, M.. 2020-11-27. Structural basis for variable IgE reactivities of Cor a 1 hazelnut allergens. https://doi.org/10.1101/2020.11.27.400978

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