Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen

Abstract : Allergy to the short ragweed (Ambrosia artemisiifolia) pollen is a major health problem. The ragweed allergen repertoire has been recently expanded with the identification of Amb a 11, a new major allergen belonging to the cysteine protease family. To better characterize Amb a 11, a recombinant proform of the molecule with a preserved active site was produced in Escherichia coli, refolded, and processed in vitro into a mature enzyme. The enzymatic activity is revealed by maturation following an autocatalytic processing resulting in the cleavage of both N- and C-terminal propeptides. The 2.05-A resolution crystal structure of pro-Amb a 11 shows an overall typical C1A cysteine protease fold with a network of molecular interactions between the N-terminal propeptide and the catalytic triad of the enzyme. The allergenicity of Amb a 11 was confirmed in a murine sensitization model, resulting in airway inflammation, production of serum IgEs, and induction of Th2 immune responses. Of note, inflammatory responses were higher with the mature form, demonstrating that the cysteine protease activity critically contributes to the allergenicity of the molecule. Collectively, our results clearly demonstrate that Amb a 11 is a bona fide cysteine protease exhibiting a strong allergenicity. As such, it should be considered as an important molecule for diagnosis and immunotherapy of ragweed pollen allergy.
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Submitted on : Tuesday, July 18, 2017 - 11:49:56 AM
Last modification on : Thursday, October 10, 2019 - 1:19:44 AM

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R. Groeme, S. Airouche, D. Kopecny, J. Jaekel, M. Savko, et al.. Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2016, 291, pp.13076--87. ⟨10.1074/jbc.M115.702001⟩. ⟨hal-01563917⟩

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