title: Multiple-mutation at a potential ligand-binding region decreased allergenicity of a mite allergen Der f 2 without disrupting global structure.
abstract: We assessed the effect of multiple-mutations within one IgE-binding area on allergenicity of Der f 2. The triple-mutant of Der f 2, P34/95/99A, exhibited the most significant reduction of allergenicity and circular dichroism analysis showed that the global structure of Der f 2 was maintained in P34/95/99A. These results indicate that such a strategy is effective when designing allergen-vaccines, which achieve less allergenicity for a broad population of patients without disrupting the global structure. Structurally, Der f 2 is a member of the MD-2 related lipid-recognition proteins. The sites for the triple-mutation located on the characteristically charged entrance of a cavity and corresponded to the regions critical to ligand-binding in the Niemann-Pick type 2 disease protein and MD-2.
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Takai
authors.forename: Hideki
authors.initials: H
authors.lastname: Hatanaka
authors.forename: Eri
authors.initials: E
authors.lastname: Mizuuchi
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Nagamune
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D060829:Arthropod Proteins; D001491:Basophils / Q000187:drug effects; D001665:Binding Sites / Q000235:genetics; D003001:Cloning, Molecular; D040001:Dermatophagoides farinae / Q000235:genetics; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451160:Dermatophagoides farinae antigen f 2; D008024:Ligands; D007073:Immunoglobulin E; D006493:Heparin