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

Autor: David Kopečný, Pierre Briozzo, Franck Jagic, Philippe Moingeon, Véronique Bordas-Le Floch, Sabi Airouche, Rachel Groeme, Judith Jaekel, Laurent Mascarell, Laetitia Bussières, Petra Zieglmayer, Maxime Le Mignon, Martin Savko, Nathalie Berjont, Véronique Baron-Bodo
Přispěvatelé: Stallergenes Greer (France, Antony), Palacky University Olomouc, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Institut Jean-Pierre Bourgin (IJPB), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Stallergenes, Convention Industrielles de Formation par la Recherche (CIFRE) fellowship from the Association Nationale de la Recherche et de la Technologie, National Program of Sustainability I Grant from the Czech Ministry of Education, Youth and Sports [LO1204], Moingeon, Philippe
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Models
Molecular
[SDV]Life Sciences [q-bio]
medicine.disease_cause
Crystallography
X-Ray
Biochemistry
law.invention
Mice
0302 clinical medicine
Allergen
law
Models
Cysteine Proteases
Catalytic Domain
Ambrosia artemisiifolia
Inbred BALB C
Conserved Sequence
Rhinitis
Plant Proteins
chemistry.chemical_classification
Cysteine Proteases/*chemistry/immunology
Plant/*immunology
Enzyme Precursors
Mice
Inbred BALB C
Crystallography
biology
Enzyme Precursors/*chemistry/immunology
Cysteine protease
3. Good health
Protein Structure and Folding
Recombinant DNA
Female
Ragweed
Molecular Sequence Data
03 medical and health sciences
Allergic
Catalytic triad
medicine
Animals
Amino Acid Sequence
Antigens
Protein precursor
Molecular Biology
Protein Processing
Plant Extracts
Post-Translational
Molecular
Rhinitis
Allergic
Seasonal
Plant Extracts/*immunology
Hydrogen Bonding
Cell Biology
Plant Proteins/*chemistry/immunology
Allergens
Antigens
Plant
biology.organism_classification
Seasonal/*immunology/prevention & control
Allergens/chemistry/immunology
030104 developmental biology
Enzyme
030228 respiratory system
chemistry
Immunology
Proteolysis
X-Ray
Protein Processing
Post-Translational
Zdroj: Journal of Biological Chemistry
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2016, 291, pp.13076--87. ⟨10.1074/jbc.M115.702001⟩
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2016, 291 (25), pp.13076--87. ⟨10.1074/jbc.M115.702001⟩
Journal of Biological Chemistry 25 (291), 13076-13087. (2016)
ISSN: 0021-9258
1083-351X
Popis: International audience; 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.
Databáze: OpenAIRE
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