Ascorbylation of a Reactive Cysteine in the Major Apple Allergen Mal d 1
Linda Ahammer,
Jana Unterhauser,
Reiner Eidelpes,
Christina Meisenbichler,
Bettina Nothegger,
Claudia E. Covaciu,
Valentina Cova,
Anna S. Kamenik,
Klaus R. Liedl,
Kathrin Breuker,
Klaus Eisendle,
Norbert Reider,
Thomas Letschka,
Martin Tollinger
Affiliations
Linda Ahammer
Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria
Jana Unterhauser
Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria
Reiner Eidelpes
Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria
Christina Meisenbichler
Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria
Bettina Nothegger
Department of Dermatology, Venerology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, Austria
Claudia E. Covaciu
Department of Dermatology, Venerology and Allergology, Central Teaching Hospital, 39100 Bolzano, Italy
Valentina Cova
Department of Applied Genomics and Molecular Biology, Laimburg Research Centre, 39040 Auer, Italy
Anna S. Kamenik
Institute of General, Inorganic and Theoretical Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria
Klaus R. Liedl
Institute of General, Inorganic and Theoretical Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria
Kathrin Breuker
Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria
Klaus Eisendle
Department of Dermatology, Venerology and Allergology, Central Teaching Hospital, 39100 Bolzano, Italy
Norbert Reider
Department of Dermatology, Venerology and Allergology, Medical University of Innsbruck, 6020 Innsbruck, Austria
Thomas Letschka
Department of Applied Genomics and Molecular Biology, Laimburg Research Centre, 39040 Auer, Italy
Martin Tollinger
Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria
The protein Mal d 1 is responsible for most allergic reactions to apples (Malus domestica) in the northern hemisphere. Mal d 1 contains a cysteine residue on its surface, with its reactive side chain thiol exposed to the surrounding food matrix. We show that, in vitro, this cysteine residue is prone to spontaneous chemical modification by ascorbic acid (vitamin C). Using NMR spectroscopy and mass spectrometry, we characterize the chemical structure of the cysteine adduct and provide a three-dimensional structural model of the modified apple allergen. The S-ascorbylated cysteine partially masks a major IgE antibody binding site on the surface of Mal d 1, which attenuates IgE binding in sera of apple-allergic patients. Our results illustrate, from a structural perspective, the role that chemical modifications of allergens with components of the natural food matrix can play.
