Background: Der p 1 is a 25-kd allergen with cysteine protease activity. Sensitization to Der p 1 affects a large proportion of individuals with allergy, resulting in rhinitis, asthma, and/or atopic dermatitis.
Objective: We determined the Der p 1 crystallographic structure to understand the relationships among structure, function, and allergenicity.
Methods: Recombinant pro-Der p 1 was produced in Pichia pastoris and allowed to mature spontaneously before purification by a 2-step procedure. Protease activity was checked by using a fluorogenic peptide substrate. Allergenicity was analysed by IgE binding assays and basophil activation test. The determination of the 3-dimensional structure was obtained by X-ray crystallography at 1.9 A resolution.
Results: The recombinant protein is fully active and expresses an allergenicity equivalent to its natural counterpart. Der p 1 exhibits a cysteine protease fold typical of the papain family, has a magnesium binding site, and forms dimers with a large interface. The crystal lattice shows that the dimers are tightly packed in a compact double layer of proteins. Such an assembly likely exists in dry fecal pellets, the natural form of allergen exposure, and appears ideal to interact with cell surface and trigger allergic inflammation.
Conclusion: We present here the 3-dimensional structural features of mature fully active Der p 1, one of the main allergens involved in human allergic diseases. This opens the possibility to evaluate the importance of enzymatic activity in pathology and possible new therapeutic interventions.
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