1XKG

Crystal structure of the major house dust mite allergen Der p 1 in its pro form at 1.61 A resolution

Summary for 1XKG

• Entry DOI: 10.2210/pdb1xkg/pdb
• Descriptor: Major mite fecal allergen Der p 1, YTTRIUM (III) ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: major allergen, cysteine protease, house dust mite, dermatophagoides pteronyssinus, inactive mutant, pro peptide, hydrolase
• Biological source: Dermatophagoides pteronyssinus (European house dust mite)
• Cellular location: Secreted: P08176
• Total number of polymer chains: 1
• Total formula weight: 35889.37

Authors

Meno, K.,Thorsted, P.B.,Gajhede, M. (deposition date: 2004-09-29, release date: 2005-06-28, Last modification date: 2024-11-20)

Primary citation

Meno, K.,Thorsted, P.B.,Ipsen, H.,Kristensen, O.,Larsen, J.N.,Spangfort, M.D.,Gajhede, M.,Lund, K.
The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen.
J.Immunol., 175:3835-3845, 2005

PubMed Abstract: 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.

PubMed: 16148130

Experimental method

X-RAY DIFFRACTION (1.61 Å)