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

J Biol Chem. 2008 Nov 7;283(45):30606-17. doi: 10.1074/jbc.M803041200. Epub 2008 Aug 25.


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 T(P1)R.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Dermatophagoides / chemistry*
  • Antigens, Dermatophagoides / genetics
  • Arthropod Proteins
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / genetics
  • Dermatophagoides pteronyssinus / enzymology*
  • Dermatophagoides pteronyssinus / genetics
  • Enzyme Activation
  • Enzyme Precursors / chemistry*
  • Enzyme Precursors / genetics
  • Glycosylation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Serine Endopeptidases


  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Enzyme Precursors
  • Recombinant Proteins
  • Dermatophagoides pteronyssinus antigen p 3
  • Serine Endopeptidases
  • Cysteine Endopeptidases
  • Dermatophagoides pteronyssinus antigen p 1