1llt
From Proteopedia
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BIRCH POLLEN ALLERGEN BET V 1 MUTANT E45S
Overview
Specific allergy vaccination is an efficient treatment for allergic, disease; however, the development of safer vaccines would enable a more, general use of the treatment. Determination of molecular structures of, allergens and allergen-Ab complexes facilitates epitope mapping and, enables a rational approach to the engineering of allergen molecules with, reduced IgE binding. In this study, we describe the identification and, modification of a human IgE-binding epitope based on the crystal structure, of Bet v 1 in complex with the BV16 Fab' fragment. The epitope occupies, approximately 10% of the molecular surface area of Bet v 1 and is clearly, conformational. A synthetic peptide representing a sequential motif in the, epitope (11 of 16 residues) did not inhibit the binding of mAb BV16 to Bet, v 1, illustrating limitations in the use of peptides for B cell epitope, characterization. The single amino acid substitution, Glu(45)-Ser, was, introduced in the epitope and completely abolished the binding of mAb BV16, to the Bet v 1 mutant within a concentration range 1000-fold higher than, wild type. The mutant also showed up to 50% reduction in the binding of, human polyclonal IgE, demonstrating that glutamic acid 45 is a critical, amino acid also in a major human IgE-binding epitope. By solving the, three-dimensional crystal structure of the Bet v 1 Glu(45)-Ser mutant, it, was shown that the change in immunochemical activity is directly related, to the Glu(45)-Ser substitution and not to long-range structural, alterations or collapse of the Bet v 1 mutant tertiary structure.
About this Structure
1LLT is a Single protein structure of sequence from Betula pendula. Full crystallographic information is available from OCA.
Reference
Dominating IgE-binding epitope of Bet v 1, the major allergen of birch pollen, characterized by X-ray crystallography and site-directed mutagenesis., Spangfort MD, Mirza O, Ipsen H, Van Neerven RJ, Gajhede M, Larsen JN, J Immunol. 2003 Sep 15;171(6):3084-90. PMID:12960334
Page seeded by OCA on Sun Nov 18 09:35:37 2007
