Der p 5 crystal structure provides insight into the group 5 dust mite allergens.
Group 5 allergens from house dust mites elicit strong IgE antibody binding in mite-allergic patients. The structure of Der p 5 was determined by x-ray crystallography to better understand the IgE epitopes, to investigate the biologic function in mites, and to compare with the conflicting published Blo t 5 structures, designated 2JMH and 2JRK in the Protein Data Bank. Der p 5 is a three-helical bundle similar to Blo t 5, but the interactions of the helices are more similar to 2JMH than 2JRK. The crystallographic asymmetric unit contains three dimers of Der p 5 that are not exactly alike. Solution scattering techniques were used to assess the multimeric state of Der p 5 in vitro and showed that the predominant state was monomeric, similar to Blo t 5, but larger multimeric species are also present. In the crystal, the formation of the Der p 5 dimer creates a large hydrophobic cavity of approximately 3000 A(3) that could be a ligand-binding site. Many allergens are known to bind hydrophobic ligands, which are thought to stimulate the innate immune system and have adjuvant-like effects on IgE-mediated inflammatory responses.
Mueller
Geoffrey A
GA
Laboratory of Structural Biology, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. mueller3@niehs.nih.gov
Gosavi
Rajendrakumar A
RA
Krahn
Joseph M
JM
Edwards
Lori L
LL
Cuneo
Matthew J
MJ
Glesner
Jill
J
Pomés
Anna
A
Chapman
Martin D
MD
London
Robert E
RE
Pedersen
Lars C
LC
D000595:Amino Acid Sequence; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D060829:Arthropod Proteins; D018360:Crystallography, X-Ray / Q000379:methods*; D008925:Mites / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451239:Dermatophagoides pteronyssinus antigen p 5