The cross-reactive calcium-binding pollen allergen, Phl p 7, reveals a novel dimer assembly.
The timothy grass pollen allergen Phl p 7 assembles most of the IgE epitopes of a novel family of 2 EF-hand calcium-binding proteins and therefore represents a diagnostic marker allergen and vaccine candidate for immunotherapy. Here we report the first three-dimensional structure of a representative of the 2 EF-hand allergen family, Phl p 7, in the calcium-bound form. The protein occurs as a novel dimer assembly with unique features: in contrast to well known EF-hand proteins such as calmodulin, parvalbumin or the S100 proteins, Phl p 7 adopts an extended conformation. Two protein monomers assemble in a head-to-tail arrangement with domain-swapped EF-hand pairing. The intertwined dimer adopts a barrel-like structure with an extended hydrophobic cavity providing a ligand-binding site. Calcium binding acts as a conformational switch between an open and a closed dimeric form of Phl p 7. These findings are interesting in the context of lipid- and calcium-dependent pollen tube growth. Furthermore, the structure of Phl p 7 allows for the rational development of vaccine strategies for treatment of sensitized allergic patients.
D000485:Allergens / Q000737:chemistry*; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D019281:Dimerization; D015195:Drug Design; D008958:Models, Molecular; D008969:Molecular Sequence Data; D031784:Phleum / Q000737:chemistry*; D010940:Plant Proteins / Q000737:chemistry*; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014612:Vaccines
D000485:Allergens; D052179:Antigens, Plant; D002135:Calcium-Binding Proteins; C468525:Phl p 7 allergen; D010940:Plant Proteins; D014612:Vaccines