Allergic cross-reactivity made visible - Solution structure of the major cherry allergen Pru av 1

Birch pollinosis is often accompanied by hypersensitivity to fruit as a con sequence of the cross-reaction of pollen allergen-specific IgE antibodies w ith homologous food proteins. To provide a basis for examining the cross-re activity on a structural level, we used heteronuclear multidimensional NMR spectroscopy to determine the high-resolution three dimensional structure o f the major cherry allergen, Flu av 1, in solution. Based on a detailed com parison of the virtually identical structures of Pru av 1 and Bet v 1, the major birch pollen allergen, we propose an explanation for a significant as pect of the observed cross-reactivity pattern among the family of allergens under consideration. The large hydrophobic cavity expected to be important for the still unknown physiological function of Bet v 1 is conserved in Pr u av 1. Structural homology to a domain of human MLN64 associated with chol esterol transport suggests phytosteroids as putative ligands for Pru av 1, NMR spectroscopy provides experimental evidence that Pru av 1 interacts wit h phytosteroids, and molecular modeling shows that the hydrophobic cavity i s large enough to accommodate two such molecules.