Activation mechanism of recombinant Der p 3 allergen zymogen: Contribution of cysteine protease Der p 1 and effect of propeptide glycosylation

Marie Eve Dumez, Nathalie Teller, Frédéric Mercier, Tetsuya Tanaka, Isabel Vandenberghe, Michel Vandenbranden, Bart Devreese, André Luxen, Jean Marie Frère, André Matagne, Alain Jacquet*, Moreno Galleni, Andy Chevigné

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

The trypsin-like protease Der p 3, a major allergen of the house dust mite Dermatophagoides pteronyssinus, is synthesized as a zymogen, termed proDer p 3. No recombinant source of Der p 3 has been described yet, and the zymogen maturation mechanism remains to be elucidated. The Der p 3 zymogen was produced in Pichia pastoris. We demonstrated that the recombinant zymogen is glycosylated at the level of its propeptide.We showed that the activation mechanism of proDer p 3 is intermolecular and is mediated by the house dust mite cysteine protease Der p 1. The primary structure of the proDer p 3 propeptide is associated with a unique zymogen activation mechanism, which is different from those described for the trypsin-like family and relies on the house dust mite papain-like protease Der p 1. This is the first report of a recombinant source of Der p 3, with the same enzymatic activity as the natural enzyme and trypsin. Glycosylation of the propeptide was found to decrease the rate of maturation. Finally, we showed that recombinant Der p 3 is inhibited by the free modified prosequence TP1R.

Original languageEnglish
Pages (from-to)30606-30617
Number of pages12
JournalJournal of Biological Chemistry
Volume283
Issue number45
DOIs
Publication statusPublished - 7 Nov 2008
Externally publishedYes

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