TERTIARY STRUCTURE OF THE MAJOR HOUSE-DUST MITE ALLERGEN DER-P-2 - SEQUENTIAL AND STRUCTURAL HOMOLOGIES

Sensitization to indoor allergens, especially those of the house dust mite, is strongly correlated with the development of asthma. We report the tertiary structure of the major house dust mite allergen, Der p 2 , determined by NMR methods. The structure of Der p 2 is a P-barrel an d is composed of two three-stranded antiparallel P-pleated sheets. Thi s arrangement of beta-strands is similar to the immunoglobulin fold wi th respect to the orientation of the two sheets and the interactions o f the strands. However, the three-dimensional structure of Der p 2 ali gns equivalently with a number of proteins from different families wit hin the immunoglobulin superfamily. The structural homology with the h ighest significance score from analysis by DALI is to Der f 2. Althoug h Der p 2 and Der f 2 are 87% identical in amino acid sequence, they a lign in three dimensions rather poorly (4.85 Angstrom RMSD; Z-score, 8 .58). This unexpected finding is likely due to the different solution conditions used during structure determination by NMR for both protein s. While the structural comparisons did not elucidate a clear homologu e for the function of Der p 2 in mites, we report that Der p 2 is sequ entially homologous to esrl6. This is a protein from moths that is exp ressed coincident with molting. Thus, this homology has important rami fications for the study of mite allergy. The structure of Der p 2 prov ides a useful tool in the design of recombinant immunotherapeutics for the group 2 allergens.