NMR structure reveals intramolecular regulation mechanism for pheromone binding and release

Odorants are transmitted by small hydrophobic molecules that cross the aque ous sensillar lymph surrounding the dendrites of the olfactory neurons to s timulate the olfactory receptors. In insects, the transport of pheromones, which are a special class of odorants, is mediated by pheromone-binding pro teins (PBPs), which occur at high concentrations in the sensillar lymph. Th e PBP from the silk moth Bombyx mori (BmPBP) undergoes a pH-dependent confo rmational transition between the forms BmPBP(A) present at pH 4.5 and BmPBP (B) present at pH 6.5. Here, we describe the NMR structure of BmPBPA, which consists of a tightly packed arrangement of seven alpha -helices linked by well defined peptide segments and knitted together by three disulfide brid ges. A scaffold of four alpha -helices that forms the ligand binding site i n the crystal structure of a BmPBP-pheromone complex is preserved in BMPBPA . The C-terminal dodecapeptide segment, which is in an extended conformatio n and located on the protein surface in the pheromone complex, forms a regu lar helix, alpha (7), which is located in the pheromone-binding site in the core of the unliganded BmPBP(A). Because investigations by others indicate that the pH value near the membrane surface is reduced with respect to the bulk sensillar lymph, the pH-dependent conformational transition of BmPBP suggests a novel physiological mechanism of intramolecular regulation of pr otein function, with the formation of alpha7 triggering the release of the pheromone from BmPBP to the membrane-standing receptor.