title: A major IgE epitope-containing grass pollen allergen domain from Phl p 5 folds as a four-helix bundle.
abstract: Phl p 5, a 29 kDa major allergen from timothy grass pollen, is one of the most reactive members of group 5 allergens. Its sequence comprises two repeats of a novel alanine-rich motif (AR) whose structure and allergenic response are still mostly unknown. We report here a structural characterization of an immunodominant fragment of Phl p 5, Phl p 5(56-165) which comprises the first AR repeat. Recombinant (r)Phl p 5(56-165) was expressed in Escherichia coli, purified to homogeneity and shown to be sufficient to react with serum IgE from 90% of grass pollen allergic patients. Using NMR spectroscopy, we show conclusively that the fragment forms a compact globular domain which is, however, prone to degradation with time. The rPhl p 5(56-165) fold consists of a four-helix bundle held together by hydrophobic interactions between the aromatic rings and aliphatic side chains. This evidence gives clear indications about the structure of the full-length Phl p 5 and provides a rational basis for finding ways to stabilize the fold and designing therapeutic vaccines against grass pollen allergy.
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001667:Binding, Competitive; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D000485:Allergens; D000939:Epitopes; D007074:Immunoglobulin G; C076049:Phl p V protein, Phleum pratense; D010940:Plant Proteins; D007073:Immunoglobulin E