A covalent recognition strategy enables conspecific mate identification

The olfactory system can detect an uncountable number of volatile molecules while retaining the ability to discriminate amongst very similar ones. We identified a unique mechanism employed by insect odorant receptors to discriminate amongst pheromones, chemical communication signals that orchestrate courtship and mating behavior. By coupling cryogenic electron microscopy (cryo-EM) and functional mutagenesis, we find that males of the silkmoth Bombyx mori distinguish between two quasi-identical compounds -bombykol, an alcohol, and bombykal, an aldehyde- by establishing a reversible covalent bond between the pheromone receptor and bombykal. Bombykol, instead, binds to the same receptor through hydrogen bonds, with significantly lower potency. The unique ability of aldehydes to establish a reversible covalent bond allows moths to unequivocally distinguish between compounds that differ only in the presence of a single hydrogen atom. Further, as many important odorants are aldehydes, this work illuminates a new binding mode available to the olfactory system to achieve high selectivity for these compounds.