The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen

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Kåre Meno, Peter B Thorsted, Henrik Ipsen, Ole Kristensen, Jørgen Larsen, Michael D Spangfort, Michael Gajhede, Kaare Lund

Allergy to house dust mite is among the most prevalent allergic diseases worldwide. Most house dust mite allergic patients react to Der p 1 from Dermatophagoides pteronyssinus, which is a cysteine protease. To avoid heterogeneity in the sample used for crystallization, a modified recombinant molecule was produced. The sequence of the proDer p 1 allergen was modified to reduce glycosylation and to abolish enzymatic activity. The resulting rproDer p 1 preparation was homogenous and stable and yielded crystals diffracting to a resolution of 1.61 A. The active site is located in a large cleft on the surface of the molecule. The 80-aa pro-peptide adopts a unique fold that interacts with the active site cleft and a substantial adjacent area on the mature region, excluding access to the cleft and the active site. Studies performed using crossed-line immunoelectrophoresis and IgE inhibition experiments indicated that several epitopes are covered by the pro-peptide and that the epitopes on the recombinant mature molecule are indistinguishable from those on the natural one. The structure confirms previous results suggesting a preference for aliphatic residues in the important P2 position in substrates. Sequence variations in related species are concentrated on the surface, which explains the existence of cross-reacting and species-specific antibodies. This study describes the first crystal structure of one of the clinically most important house dust mite allergens, the cysteine protease Der p 1.
Original languageEnglish
JournalJournal of Immunology
Volume175
Issue number6
Pages (from-to)3835-45
Number of pages11
ISSN0022-1767
Publication statusPublished - 2005

    Research areas

  • Allergens, Animals, Arthropod Proteins, Binding Sites, Cross Reactions, Crystallography, X-Ray, Epitopes, Genetic Engineering, Models, Molecular, Molecular Structure, Protein Conformation, Protein Precursors, Pyroglyphidae, Recombinant Proteins, Species Specificity, Substrate Specificity

ID: 40318507