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 beta-barrel and is composed of two three-stranded antiparallel beta-pleated sheets. This arrangement of beta-strands is similar to the immunoglobulin fold with respect to the orientation of the two sheets and the interactions of the strands. However, the three-dimensional structure of Der p 2 aligns equivalently with a number of proteins from different families within the immunoglobulin superfamily. The structural homology with the highest significance score from analysis by DALI is to Der f 2. Although Der p 2 and Der f 2 are 87% identical in amino acid sequence, they align in three dimensions rather poorly (4.85 A RMSD; Z-score, 8.58). This unexpected finding is likely due to the different solution conditions used during structure determination by NMR for both proteins. While the structural comparisons did not elucidate a clear homologue for the function of Der p 2 in mites, we report that Der p 2 is sequentially homologous to esr16. This is a protein from moths that is expressed coincident with molting. Thus, this homology has important ramifications for the study of mite allergy. The structure of Der p 2 provides a useful tool in the design of recombinant immunotherapeutics for the group 2 allergens.
Mueller
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GA
Beirne B. Carter Center for Immunology, the Asthma and Allergic Disease Center, University of Virginia, Charlottesville 22908, USA.
Benjamin
D C
DC
Rule
G S
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D000485:Allergens / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D039741:Antigens, Dermatophagoides; D018360:Crystallography, X-Ray; D004391:Dust; D006023:Glycoproteins / Q000737:chemistry*; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007136:Immunoglobulins / Q000737:chemistry; D019476:Insect Proteins / Q000737:chemistry; D008925:Mites / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
D000485:Allergens; D039741:Antigens, Dermatophagoides; D004391:Dust; C100022:ESR16 protein, Manduca sexta; D006023:Glycoproteins; D007136:Immunoglobulins; D019476:Insect Proteins