title: Crystal structure of the major celery allergen Api g 1: molecular analysis of cross-reactivity.
abstract: Many patients who have been sensitised to pollen, display allergic symptoms after ingestion of certain plant food such as fresh fruit, vegetables and nuts. The cause is the cross-reactivity between structurally very similar major plant allergens. In particular, allergy to celery is very frequently associated with birch and mugwort pollen sensitization, known as to the birch-mugwort-celery syndrome. The crystal structure of the major celery allergen Api g 1, a homologue of the major birch pollen allergen Bet v 1, has been determined to a resolution of 2.9 A. The structure of Api g 1 is very similar to that of Bet v 1 with major differences occurring in the segment comprised of residues 23-45, preceding the well conserved glycine-rich P-loop, as well as in loops beta3-beta4 and beta5-beta6. In particular, Api g 1 lacks E45, which has been shown to be a crucial residue for antibody recognition in the crystal complex of Bet v 1 with the Fab fragment of a murine monoclonal IgG (BV16) antibody. The absence of E45 and the structural differences in the preceding segment suggest that this region of the Api g 1 surface is probably not responsible for the observed cross-reactivity with Bet v 1. A detailed analysis of the molecular surface in combination with sequence alignment revealed three conserved surface patches which may account for cross-reactivity with Bet v 1. Several residues of Bet v 1 which have been shown by mutagenesis studies to be involved in IgE recognition belong to these conserved surface regions. The structure of Api g 1 and the related epitope analysis provides a molecular basis for a better understanding of allergen cross-reactivity and may lead to the development of hypoallergens which would allow a safer immunotherapy.
authors.affiliation: Department of Structural Biology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Tilman
authors.initials: T
authors.lastname: Schirmer
authors.forename: Karin
authors.initials: K
authors.lastname: Hoffimann-Sommergrube
authors.forename: Markus
authors.initials: M
authors.lastname: Susani
authors.forename: Heimo
authors.initials: H
authors.lastname: Breiteneder
authors.forename: Zora
authors.initials: Z
authors.lastname: Marković-Housley
mesh_terms: D000485:Allergens / Q000737:chemistry*; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D000077102:Apium; D018360:Crystallography, X-Ray / Q000379:methods*; D000939:Epitopes / Q000737:chemistry; D005512:Food Hypersensitivity; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010940:Plant Proteins / Q000737:chemistry*; D011058:Pollen; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D000485:Allergens; D052179:Antigens, Plant; C477756:Api g 5 allergen, celery; D000939:Epitopes; D010940:Plant Proteins; C479400:Pru av 1 allergen, Prunus avium; D007073:Immunoglobulin E