A Ligand, Not a Carrier

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Science  11 Jul 2008:
Vol. 321, Issue 5886, pp. 177
DOI: 10.1126/science.321.5886.177c

Volatile odorants are generally thought to bind to G protein-coupled receptors, and this event then activates downstream signaling pathways. In Drosophila, various odorant-binding proteins are secreted into the lymph around subsets of olfactory neurons; the function of these pheromone- and odorant-binding proteins, however, has been unclear. Building on earlier work that showed that the odorant-binding protein LUSH is required for sensitivity to the pheromone 11-cis vaccenyl acetate (cVA), Laughlin et al. have compared the x-ray crystal structure of LUSH bound to cVA with the previously determined structure of uncomplexed LUSH and found that binding of cVA (which was almost completely enclosed by LUSH) induced a conformational change in LUSH. A LUSH mutant bearing an amino acid substitution predicted to minimize this conformational change was less effective than the wild-type protein at conferring cVA sensitivity to T1 neurons, which mediate the response to this pheromone; in contrast, a mutation predicted to enhance the conformational change produced a more potent ligand. Moreover, a mutation yielding an uncomplexed LUSH conformation that resembled that of the cVA-bound form stimulated T1 neurons even in the absence of cVA. Thus, the authors conclude that LUSH is an inactive ligand that is converted into an active form through cVA binding. — EMA

Cell 133, 1255 (2008).

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