Der p 1 is the primary activator of der p 3, der p 6 and der p 9 the proteolytic allergens produced by the house dust mite Dermatophagoides pteronyssinus

Julie Herman, Nicolas Thelen, Nicolas Smargiasso, Anne Catherine Mailleux, André Luxen, Marie Cloes, Edwin De Pauw, Andy Chevigné, Moreno Galleni*, Marie Eve Dumez

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    26 Citations (Scopus)

    Abstract

    Background The enzymatic activity of the four proteases found in the house dust mite Dermatophagoides pteronyssinus is involved in the pathogenesis of allergy. Our aim was to elucidate the activation cascade of their corresponding precursor forms and particularly to highlight the interconnection between proteases during this cascade. Methods The cleavage of the four peptides corresponding to the mite zymogen activation sites was studied on the basis of the Förster Resonance Energy Transfer method. The proDer p 6 zymogen was then produced in Pichia pastoris to elucidate its activation mechanism by mite proteases, especially Der p 1. The role of the propeptide in the inhibition of the enzymatic activity of Der p 6 was also examined. Finally, the Der p 1 and Der p 6 proteases were localised via immunolocalisation in D. pteronyssinus. Results All peptides were specifically cleaved by Der p 1, such as proDer p 6. The propeptide of proDer p 6 inhibited the proteolytic activity of Der p 6, but once cleaved, it was degraded by the protease. The Der p 1 and Der p 6 proteases were both localised to the midgut of the mite. Conclusions Der p 1 in either its recombinant form or in the natural context of house dust mite extracts specifically cleaves all zymogens, thus establishing its role as a major activator of both mite cysteine and serine proteases. General significance This finding suggests that Der p 1 may be valuable target against mites.

    Original languageEnglish
    Pages (from-to)1117-1124
    Number of pages8
    JournalBiochimica et Biophysica Acta - General Subjects
    Volume1840
    Issue number3
    DOIs
    Publication statusPublished - Mar 2014

    Keywords

    • Dermatophagoides pteronyssinus
    • Digestion
    • Mite allergen
    • Protease

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