NMR structure reveals intramolecular regulation mechanism for pheromone binding and release

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The National Academy of Sciences

RESUMO

Odorants are transmitted by small hydrophobic molecules that cross the aqueous sensillar lymph surrounding the dendrites of the olfactory neurons to stimulate the olfactory receptors. In insects, the transport of pheromones, which are a special class of odorants, is mediated by pheromone-binding proteins (PBPs), which occur at high concentrations in the sensillar lymph. The PBP from the silk moth Bombyx mori (BmPBP) undergoes a pH-dependent conformational transition between the forms BmPBPA present at pH 4.5 and BmPBPB present at pH 6.5. Here, we describe the NMR structure of BmPBPA, which consists of a tightly packed arrangement of seven α-helices linked by well defined peptide segments and knitted together by three disulfide bridges. A scaffold of four α-helices that forms the ligand binding site in the crystal structure of a BmPBP–pheromone complex is preserved in BmPBPA. The C-terminal dodecapeptide segment, which is in an extended conformation and located on the protein surface in the pheromone complex, forms a regular helix, α7, which is located in the pheromone-binding site in the core of the unliganded BmPBPA. 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 protein function, with the formation of α7 triggering the release of the pheromone from BmPBP to the membrane-standing receptor.

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