PDBsum entry 5ef4

Allergen

PDB id: 5ef4

Contents

Protein chains

328 a.a.

Ligands

GOL ×4

Waters ×282

PDB id:

5ef4

Name:

Allergen

Title:

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

Structure:

Cysteine protease. Chain: a, b. Fragment: unp residues 23-386. Engineered: yes

Source:

Ambrosia artemisiifolia. Short ragweed. Organism_taxid: 4212. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.05Å R-factor: 0.172 R-free: 0.199

Authors:

P.Briozzo,D.Kopecny,M.Savko

Key ref:

R.Groeme et al. (2016). Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen. J Biol Chem, 291, 13076-13087. PubMed id: 27129273 DOI: 10.1074/jbc.M115.702001

Date:

23-Oct-15 Release date: 27-Apr-16

Protein chains

V5LU01  (CEP01_AMBAR) -  Cysteine protease Amb a 11.0101 from Ambrosia artemisiifolia

Seq: 386 a.a.

Struc: 328 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.22.- - ?????

DOI no: 10.1074/jbc.M115.702001

J Biol Chem 291:13076-13087 (2016)

PubMed id: 27129273

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

R.Groeme, S.Airouche, D.Kopečný, J.Jaekel, M.Savko, N.Berjont, L.Bussieres, M.Le Mignon, F.Jagic, P.Zieglmayer, V.Baron-Bodo, V.Bordas-Le Floch, L.Mascarell, P.Briozzo, P.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, 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.