An immunoglobulin-like fold in a major plant allergen: the solution structure of Phl p 2 from timothy grass pollen

Background: Grass pollen allergens are the most important and widespread el icitors of pollen allergy. One of the major plant allergens which millions of people worldwide are sensitized to is Phl p 2, a small protein from timo thy grass pollen. Phl p 2 is representative of the large family of cross-re acting plant allergens classified as group 2/3, Recombinant Phl p 2 has bee n demonstrated by immunological cross-reactivity studies to be immunologica lly equivalent to the natural protein. Results: We have solved the solution structure of recombinant Phl p 2 by me ans of nuclear magnetic resonance techniques. The three-dimensional structu re of Phl p 2 consists of an all-beta ford with nine antiparallel beta stra nds that form a beta sandwich, The topology is that of an immunoglobulin-li ke fold with the addition of a C-terminal strand, as found in the C2 domain superfamily. Lack of functional and sequence similarity with these two fam ilies, however, suggests an independent evolution of Phl p 2 and other homo logous plant allergens. Conclusions: Because of the high homology with other plant allergens of gro ups 1 and 2/3, the structure of Phl p 2 can be used to rationalize some of the immunological properties of the whole family. On the basis of the struc ture, we suggest possible sites of interaction with IgE antibodies. Knowled ge of the Phl p 2 structure may assist the rational structure-based design of synthetic vaccines against grass pollen allergy.