Interactions between mature Der p 1 and its free prodomain indicate membership of a new family of C1 peptidases

J. Zhang, J. M. Hamilton, D. R. Garrod, C. Robinson

    Research output: Contribution to journalArticlepeer-review


    Background: Studies in vivo have shown that the cysteine peptidase activity of group 1 house dust mite allergens contributes to their allergenicity. These allergens are synthesized initially as proenzymes and removal of the propiece is necessary to unmask their proteolytic activity. In related C1 family cysteine peptidases of enzyme clan CA, liberated propieces continue to inhibit the mature peptidase as tight binding inhibitors. As it is not known whether mite peptidase allergens behave similarly, our objective was to investigate the effect of the Der p 1 propiece on the catalytic activity of Der p 1 and Der f 1. Methods: Enzymatic activity of natural Der p 1 and Der f 1 was assessed using a specific substrate and the effect of the recombinant propiece on its enzyme kinetics defined. The integrity of the propiece during these interactions was studied functionally and by analysis of the reaction mixtures. Results: Der p 1 propiece was a potent competitive inhibitor of Der p 1 and Der f 1. In contrast to other cysteine peptidase prodomains, which are cognate tight binding inhibitors, the Der p 1 propiece behaves as a substrate and is fully degraded during this interaction. Conclusion: Mature Der p 1-prodomain interactions differ from other C1 family cysteine peptidases, suggesting that group 1 mite allergens are a new subgroup among C1 family cysteine peptidases. The rapid inactivation of Der p 1 prodomain is a newly identified mechanism that may contribute to the potency of this allergen. © 2007 The Authors.
    Original languageEnglish
    Pages (from-to)1302-1309
    Number of pages7
    JournalAllergy: European Journal of Allergy and Clinical Immunology
    Issue number11
    Publication statusPublished - Nov 2007


    • Cysteine protease
    • Der p 1
    • Dust mite allergy
    • Peptidase allergen


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