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.

• MeSH
• alergeny chemie   imunologie   MeSH
• antigeny rostlinné imunologie   MeSH
• cysteinové proteasy chemie   imunologie   MeSH
• katalytická doména MeSH
• konzervovaná sekvence MeSH
• krystalografie rentgenová MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• myši inbrední BALB C MeSH
• posttranslační úpravy proteinů MeSH
• prekurzory enzymů chemie   imunologie   MeSH
• proteolýza MeSH
• rostlinné extrakty imunologie   MeSH
• rostlinné proteiny chemie   imunologie   MeSH
• sekvence aminokyselin MeSH
• sezónní alergická rýma imunologie   prevence a kontrola   MeSH
• vodíková vazba MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH