Title |
Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen*
|
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Published in |
Journal of Biological Chemistry, April 2016
|
DOI | 10.1074/jbc.m115.702001 |
Pubmed ID | |
Authors |
Rachel Groeme, Sabi Airouche, David Kopečný, Judith Jaekel, Martin Savko, Nathalie Berjont, Laetitia Bussieres, Maxime Le Mignon, Franck Jagic, Petra Zieglmayer, Véronique Baron-Bodo, Véronique Bordas-Le Floch, Laurent Mascarell, Pierre Briozzo, Philippe Moingeon |
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 Å 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 as well as 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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Student > Bachelor | 6 | 19% |
Researcher | 4 | 13% |
Student > Master | 3 | 9% |
Student > Doctoral Student | 2 | 6% |
Other | 1 | 3% |
Unknown | 9 | 28% |
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Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
Other | 3 | 9% |
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