W0458

Structural Studies of Bombyx mori Pheromone Binding Protein and their Implications for Protein Specificity and Pheromone Release. Catherine Lautenschlager, Dept. of Molecular Biology and Genetics, Cornell Univ., Ithaca, NY 14853, and Jon Clardy, Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.

Insects, and invertebrates in general, need pheromone binding proteins (PBPs) to transport hydrophobic pheromones to G-protein-linked receptors. The degree to which PBPs can discriminate between pheromone-like ligands is a matter of debate. These pheromones are very hydrophobic, the binding proteins small and highly charged; this incompatibility has complicated attempts to directly measure K_d values. The X-ray crystal structures of two new complexes, B. mori PBP with iodohexadecane and with bell pepper odorant (a flat, aromatic molecule), were determined at resolutions of 1.9 Å and 2.0 Å, respectively. In both structures the PBP maintains a conformation similar to that seen when bound to the sex pheromone bombykol (1), data that has only been obtained through crystallography.

The crystal structure of unliganded B. mori PBP at pH 7.5 was determined at a resolution of 2.3 Å. In this crystal structure, the PBP assumes a conformation with the C-terminal region of the protein forming an ordered helix occupying the binding pocket. These data suggest B. mori PBP may undergo a ligand-dependent comformational change in addition to the previously described pH-dependent conformational change, data only seen by crystallography.