Ascorbylation of a Reactive Cysteine in the Major Apple Allergen Mal d 1
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Identification and Characterization of Mal d 1 Ascorbylation
3.2. Structure of Ascorbylated Mal d 1
3.3. Effect of Mal d 1 Ascorbylation on Antibody Binding
4. Discussion and Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Geroldinger-Simic, M.; Zelniker, T.; Aberer, W.; Ebner, C.; Egger, C.; Greiderer, A.; Prem, N.; Lidholm, J.; Ballmer-Weber, B.K.; Vieths, S.; et al. Birch pollen-related food allergy: Clinical aspects and the role of allergen-specific IgE and IgG4 antibodies. J. Allergy Clin. Immunol. 2011, 127, 616–622. [Google Scholar] [CrossRef]
- Chebib, S.; Meng, C.; Ludwig, C.; Bergmann, K.C.; Becker, S.; Dierend, W.; Schwab, W. Identification of allergenomic signatures in allergic and well-tolerated apple genotypes using LC-MS/MS. Food Chem. 2022, 4, 100111. [Google Scholar] [CrossRef]
- Ahammer, L.; Grutsch, S.; Kamenik, A.S.; Liedl, K.R.; Tollinger, M. Structure of the major apple allergen Mal d 1. J. Agric. Food Chem. 2017, 65, 1606–1612. [Google Scholar] [CrossRef] [PubMed]
- Romer, E.; Chebib, S.; Bergmann, K.C.; Plate, K.; Becker, S.; Ludwig, C.; Meng, C.; Fischer, T.; Dierend, W.; Schwab, W. Tiered approach for the identification of Mal d 1 reduced, well tolerated apple genotypes. Sci. Rep. 2020, 10, 9144. [Google Scholar] [CrossRef]
- Vegro, M.; Eccher, G.; Populin, F.; Sorgato, C.; Savazzini, F.; Pagliarani, G.; Tartarini, S.; Pasini, G.; Curioni, A.; Antico, A.; et al. Old apple (Malus domestica L. Borkh.) varieties with hypoallergenic properties: An integrated approach for studying apple allergenicity. J. Agric. Food Chem. 2016, 64, 9224–9236. [Google Scholar] [CrossRef]
- Son, D.Y.; Scheurer, S.; Hoffmann, A.; Haustein, D.; Vieths, S. Pollen-related food allergy: Cloning and immunological analysis of isoforms and mutants of Mal d 1, the major apple allergen, and Bet v 1, the major birch pollen allergen. Eur. J. Nutr. 1999, 38, 201–215. [Google Scholar] [CrossRef]
- Aglas, L.; Soh, W.T.; Kraiem, A.; Wenger, M.; Brandstetter, H.; Ferreira, F. Ligand binding of PR-10 proteins with a particular focus on the Bet v 1 allergen family. Curr. Allergy Asthma Rep. 2020, 20, 25. [Google Scholar] [CrossRef]
- Chruszcz, M.; Chew, F.; Hoffmann-Sommergruber, K.; Hurlburt, B.; Mueller, G.A.; Pomes, A.; Rouvinen, J.; Villalba, M.; Wohrl, B.; Breiteneder, H. Allergens and their associated small molecule ligands-their dual role in sensitization. Allergy 2021, 76, 2367–2382. [Google Scholar] [CrossRef] [PubMed]
- Gou, J.; Liang, R.; Huang, H.; Ma, X. Maillard reaction induced changes in allergenicity of food. Foods 2022, 11, 530. [Google Scholar] [CrossRef]
- Lemmens, E.; Alos, E.; Rymenants, M.; De Storme, N.; Keulemans, W.J. Dynamics of ascorbic acid content in apple (Malus x domestica) during fruit development and storage. Plant Physiol. Biochem. 2020, 151, 47–59. [Google Scholar] [CrossRef]
- Smirnoff, N.; Wheeler, G.L. Ascorbic acid in plants: Biosynthesis and function. Crit. Rev. Biochem. Mol. Biol. 2000, 35, 291–314. [Google Scholar] [CrossRef]
- Marzban, G.; Kinaciyan, T.; Maghuly, F.; Brunner, R.; Gruber, C.; Hahn, R.; Jensen-Jarolim, E.; Laimer, M. Impact of sulfur and vitamin C on the allergenicity of Mal d 2 from apple (Malus domestica). J. Agric. Food Chem. 2014, 62, 7622–7630. [Google Scholar] [CrossRef]
- Regulus, P.; Desilets, J.; Klarskov, K.; Wagner, J.R. Characterization and detection in cells of a novel adduct derived from the conjugation of glutathione and dehydroascorbate. Free Radic. Biol. Med. 2010, 49, 984–991. [Google Scholar] [CrossRef]
- Flandrin, A.; Allouche, S.; Rolland, Y.; McDuff, F.; Wagner, J.R.; Klarskov, K. Characterization of dehydroascorbate-mediated modification of glutaredoxin by mass spectrometry. J. Mass Spectrom. 2015, 50, 1358–1366. [Google Scholar] [CrossRef]
- Kaeswurm, J.A.H.; Nestl, B.; Richter, S.M.; Emperle, M.; Buchweitz, M. Purification and characterization of recombinant expressed apple allergen Mal d 1. Methods Protoc. 2021, 4, 3. [Google Scholar] [CrossRef]
- Ahammer, L.; Grutsch, S.; Tollinger, M. NMR resonance assignments of the major apple allergen Mal d 1. Biomol. NMR Assign. 2016, 10, 287–290. [Google Scholar] [CrossRef]
- Grutsch, S.; Fuchs, J.; Freier, R.; Kofler, S.; Bibi, M.; Asam, C.; Wallner, M.; Ferreira, F.; Brandstetter, H.; Liedl, K.R.; et al. Ligand binding modulates the structural dynamics and compactness of the major birch pollen allergen. Biophys. J. 2014, 107, 2972–2981. [Google Scholar] [CrossRef]
- Tollinger, M.; Kloiber, K.; Agoston, B.; Dorigoni, C.; Lichtenecker, R.; Schmid, W.; Konrat, R. An isolated helix persists in a sparsely populated form of KIX under native conditions. Biochemistry 2006, 45, 8885–8893. [Google Scholar] [CrossRef]
- Führer, S.; Kamenik, A.S.; Zeindl, R.; Nothegger, B.; Hofer, F.; Reider, N.; Liedl, K.R.; Tollinger, M. Inverse relation between structural flexibility and IgE reactivity of Cor a 1 hazelnut allergens. Sci. Rep. 2021, 11, 4173. [Google Scholar] [CrossRef]
- Nothegger, B.; Reider, N.; Covaciu, C.; Cova, V.; Ahammer, L.; Eidelpes, R.; Unterhauser, J.; Platzgummer, S.; Tollinger, M.; Letschka, T.; et al. Allergen-specific immunotherapy with apples: Selected cultivars could be a promising tool for birch pollen allergy. J. Eur. Acad. Dermatol. Venereol. 2020, 34, 1286–1292. [Google Scholar] [CrossRef] [PubMed]
- Nothegger, B.; Reider, N.; Covaciu, C.; Cova, V.; Ahammer, L.; Eidelpes, R.; Unterhauser, J.; Platzgummer, S.; Raffeiner, E.; Tollinger, M.; et al. Oral birch pollen immunotherapy with apples: Results of a phase II clinical pilot study. Immun. Inflamm. Dis. 2021, 9, 503–511. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Wolf, R.M.; Caldwell, J.W.; Kollman, P.A.; Case, D.A. Development and testing of a general amber force field. J. Comput. Chem. 2004, 25, 1157–1174. [Google Scholar] [CrossRef] [PubMed]
- Bayly, C.I.; Cieplak, P.; Cornell, W.; Kollman, P.A. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: The RESP model. Phys. Chem. 1993, 97, 10269–10280. [Google Scholar] [CrossRef]
- Chebib, S.; Schwab, W. Microscale thermophoresis reveals oxidized glutathione as high-affinity ligand of Mal d 1. Foods 2021, 10, 2771. [Google Scholar] [CrossRef] [PubMed]
- Führer, S.; Unterhauser, J.; Zeindl, R.; Eidelpes, R.; Fernandez-Quintero, M.L.; Liedl, K.R.; Tollinger, M. The structural flexibility of PR-10 food allergens. Int. J. Mol. Sci. 2022, 23, 8252. [Google Scholar] [CrossRef]
- Ma, Y.; Gadermaier, G.; Bohle, B.; Bolhaar, S.; Knulst, A.; Markovic-Housley, Z.; Breiteneder, H.; Briza, P.; Hoffmann-Sommergruber, K.; Ferreira, F. Mutational analysis of amino acid positions crucial for IgE-binding epitopes of the major apple (Malus domestica) allergen, Mal d 1. Int. Arch. Allergy Immunol. 2006, 139, 53–62. [Google Scholar] [CrossRef]
- Bolhaar, S.; Zuidmeer, L.; Ma, Y.; Ferreira, F.; Bruijnzeel-Koomen, C.; Hoffmann-Sommergruber, K.; van Ree, R.; Knulst, A. A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge. Clin. Exp. Allergy 2005, 35, 1638–1644. [Google Scholar] [CrossRef]
- Gieras, A.; Cejka, P.; Blatt, K.; Focke-Tejkl, M.; Linhart, B.; Flicker, S.; Stoecklinger, A.; Marth, K.; Drescher, A.; Thalhamer, J.; et al. Mapping of conformational IgE epitopes with peptide-specific monoclonal antibodies reveals simultaneous binding to a surface patch on the major birch pollen allergen. J. Immunol. 2011, 186, 5333–5344. [Google Scholar] [CrossRef]
- Kay, P.; Wagner, J.; Gagnon, H.; Day, R.; Klarskov, K. Modification of peptide and protein cysteine thiol groups by conjugation with a degradation product of ascorbate. Chem. Res. Toxicol. 2013, 26, 1333–1339. [Google Scholar] [CrossRef]
- Zhang, Y. Ascorbic Acid in Plants: Biosynthesis, Regulation and Enhancement; Springer: New York, NY, USA, 2013; p. 117. [Google Scholar]
- Cabanillas, B.; Novak, N. Effects of daily food processing on allergenicity. Crit. Rev. Food Sci. Nutr. 2019, 59, 31–42. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ahammer, L.; Unterhauser, J.; Eidelpes, R.; Meisenbichler, C.; Nothegger, B.; Covaciu, C.E.; Cova, V.; Kamenik, A.S.; Liedl, K.R.; Breuker, K.; et al. Ascorbylation of a Reactive Cysteine in the Major Apple Allergen Mal d 1. Foods 2022, 11, 2953. https://doi.org/10.3390/foods11192953
Ahammer L, Unterhauser J, Eidelpes R, Meisenbichler C, Nothegger B, Covaciu CE, Cova V, Kamenik AS, Liedl KR, Breuker K, et al. Ascorbylation of a Reactive Cysteine in the Major Apple Allergen Mal d 1. Foods. 2022; 11(19):2953. https://doi.org/10.3390/foods11192953
Chicago/Turabian StyleAhammer, Linda, Jana Unterhauser, Reiner Eidelpes, Christina Meisenbichler, Bettina Nothegger, Claudia E. Covaciu, Valentina Cova, Anna S. Kamenik, Klaus R. Liedl, Kathrin Breuker, and et al. 2022. "Ascorbylation of a Reactive Cysteine in the Major Apple Allergen Mal d 1" Foods 11, no. 19: 2953. https://doi.org/10.3390/foods11192953