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Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2016 Jun 17; Vol. 291 (25), pp. 13076-87. Date of Electronic Publication: 2016 Apr 19. - Publication Year :
- 2016
-
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, 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.<br /> (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Allergens chemistry
Allergens immunology
Amino Acid Sequence
Animals
Catalytic Domain
Conserved Sequence
Crystallography, X-Ray
Cysteine Proteases immunology
Enzyme Precursors immunology
Female
Hydrogen Bonding
Mice, Inbred BALB C
Models, Molecular
Molecular Sequence Data
Plant Proteins immunology
Protein Processing, Post-Translational
Proteolysis
Rhinitis, Allergic, Seasonal prevention & control
Antigens, Plant immunology
Cysteine Proteases chemistry
Enzyme Precursors chemistry
Plant Extracts immunology
Plant Proteins chemistry
Rhinitis, Allergic, Seasonal immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 291
- Issue :
- 25
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 27129273
- Full Text :
- https://doi.org/10.1074/jbc.M115.702001