2JRK

NMR Structure and Epitope Mapping of Blo t 5

2JRK の概要

• エントリーDOI: 10.2210/pdb2jrk/pdb
• NMR情報: BMRB: 15345
• 分子名称: Mite allergen Blo t 5 (1 entity in total)
• 機能のキーワード: blo t 5, 3 helices bundle, dust mite allergen, allergen
• 由来する生物種: Blomia tropicalis (Mite)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13293.00

構造登録者

Chan, S.,Mok, Y. (登録日: 2007-06-27, 公開日: 2008-07-01, 最終更新日: 2024-05-01)

主引用文献

Chan, S.L.,Ong, T.C.,Gao, Y.F.,Tiong, Y.S.,Wang, D.Y.,Chew, F.T.,Mok, Y.K.
Nuclear magnetic resonance structure and IgE epitopes of Blo t 5, a major dust mite allergen
J.Immunol., 181:2586-2596, 2008

PubMed Abstract: A high incidence of sensitization to Blomia tropicalis, the predominant house dust mite species in tropical regions, is strongly associated with allergic diseases in Singapore, Malaysia, and Brazil. IgE binding to the group 5 allergen, Blo t 5, is found to be the most prevalent among all B. tropicalis allergens. The NMR structure of Blo t 5 determined represents a novel helical bundle structure consisting of three antiparallel alpha-helices. Based on the structure and sequence alignment with other known group 5 dust mite allergens, surface-exposed charged residues have been identified for site-directed mutagenesis and IgE binding assays. Four charged residues, Glu76, Asp81, Glu86, and Glu91 at around the turn region connecting helices alpha2 and alpha3 have been identified to be involved in the IgE binding. Using overlapping peptides, we have confirmed that these charged residues are located on a major putative linear IgE epitope of Blo t 5 from residues 76-91 comprising the sequence ELKRTDLNILERFNYE. Triple and quadruple mutants have been generated and found to exhibit significantly lower IgE binding and reduced responses in skin prick tests. The mutants induced similar PBMC proliferation as the wild-type protein but with reduced Th2:Th1 cytokines ratio. Mass screening on a quadruple mutant showed a 40% reduction in IgE binding in 35 of 42 sera of atopic individuals. Findings in this study further stressed the importance of surface-charged residues on IgE binding and have implications in the cross-reactivity and use of Blo t 5 mutants as a hypoallergen for immunotherapy.

PubMed: 18684949

実験手法

SOLUTION NMR