The Crystal Structure of a Major Dust Mite Allergen Der p 2, and its Biological Implications (1)
The house dust mite allergen, Der p 2, is a major allergen and 80–90% of patients who react to mite extract, react specifically to this protein or its homologues. The overall tertiary fold of Der p 2 is that of two anti-parallel b-pleated sheets overlying each other at an angle of approximately 30 degree. This fold is characteristic of the immunoglobulin superfamily and Der p 2 appears to belong to the E-set domain subfamily. The molecule contains ten b-strands and a short (one-turn) 310 helix. There are three disulfide bonds in Der p 2 forming covalent bonds between residues 21 and 27, 73 and 78, and 8 and 119. The ligand molecules must be hydrophobic because the cavity is lined with hydrophobic and aromatic amino acid residues. Sheet II contributes the following: strand G, Ala118, Ala120 and Ala122; strand F, Val104, Val106, Val108, Val110 and strand C, Ile52, Ile54 and Ile58 and Ala56.
Almost all the IgE anti-Der p 2 antibodies from several allergic patients are directed toward two of these antigenic regions suggesting that the Der p 2 allergen in humans is paucivalent rather than polyvalent.
The original crystals of Der p 2 were obtained from the same protein samples that were used in our NMR experiments. There are nuclear Overhauser effects (NOEs) between the b-sheets at the center of the hydrophobic cavity and, specifically, dipolar coupling was observed between residues 37 and 106, 37 and 108, and 52 and 88. In mites Der p 2 serves a biological function involving binding and/or transport of a lipid-like molecule.
