5EF4

2.05 A crystal structure of the Amb a 11 cysteine protease, a major ragweed pollen allergen, in its proform

5EF4 の概要

• エントリーDOI: 10.2210/pdb5ef4/pdb
• 分子名称: Cysteine protease, GLYCEROL (3 entities in total)
• 機能のキーワード: allergen, ragweed, cysteine protease, propeptide
• 由来する生物種: Ambrosia artemisiifolia (Short ragweed)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 86531.32

構造登録者

Briozzo, P.,Kopecny, D.,Savko, M. (登録日: 2015-10-23, 公開日: 2016-04-27, 最終更新日: 2024-11-06)

主引用文献

Groeme, R.,Airouche, S.,Kopecny, D.,Jaekel, J.,Savko, M.,Berjont, N.,Bussieres, L.,Le Mignon, M.,Jagic, F.,Zieglmayer, P.,Baron-Bodo, V.,Bordas-Le Floch, V.,Mascarell, L.,Briozzo, P.,Moingeon, P.
Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen.
J.Biol.Chem., 291:13076-13087, 2016

PubMed 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.

PubMed: 27129273
DOI: 10.1074/jbc.M115.702001

実験手法

X-RAY DIFFRACTION (2.05 Å)