1LLT

BIRCH POLLEN ALLERGEN BET V 1 MUTANT E45S

Summary for 1LLT

• Entry DOI: 10.2210/pdb1llt/pdb
• Related: 1BTV 1BV1 1FSK 1QMR
• Descriptor: POLLEN ALLERGEN BET V 1 (1 entity in total)
• Functional Keywords: allergen, pathogenesis related proteins
• Biological source: Betula pendula (European white birch)
• Cellular location: Cytoplasm: P15494
• Total number of polymer chains: 1
• Total formula weight: 17385.54

Authors

Spangfort, M.D.,Mirza, O.,Ipsen, H.,Van Neerven, R.J.,Gajhede, M.,Larsen, J.N. (deposition date: 2002-04-30, release date: 2003-10-28, Last modification date: 2024-02-14)

Primary citation

Spangfort, M.D.,Mirza, O.,Ipsen, H.,Van Neerven, R.J.,Gajhede, M.,Larsen, J.N.
Dominating IgE-binding epitope of Bet v 1, the major allergen of birch pollen, characterized by X-ray crystallography and site-directed mutagenesis.
J.Immunol., 171:3084-3090, 2003

PubMed Abstract: 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.

PubMed: 12960334

Experimental method

X-RAY DIFFRACTION (3.1 Å)