Sensing Scents: Structural Insights into Insect Olfactory Receptors

Abstract

The olfactory system must detect and discriminate amongst the enormous diversity of chemicals in the environment. To contend with this challenge, insects have evolved a large family of heteromeric odorant-gated ion channels comprised of a highly conserved co-receptor (Orco) and a highly divergent odorant receptor (OR) that confers chemical specificity. ORs are very diverse in sequence, reflecting their rapid diversification to allow each insect species to adapt to its specific ecological and chemical niche. To gain insight into how chemical detection is mediated in this unique channel family, we used cryo-electron microscopy to elucidate the structure of an Orco homomer at 3.5 Å resolution. Orco possesses a novel channel architecture, with four subunits symmetrically arranged around a central pore. The Orco tetramer has few inter-subunit interactions within the membrane and is bound together largely by a small cytoplasmic anchor domain. The minimal sequence conservation among ORs maps largely to the pore and anchor domain, revealing how the architecture of this receptor family accommodates its remarkable sequence diversity and facilitates the evolution of odor tuning. Additional structures from this family are beginning to shed light on the molecular determinants of ligand binding and how these receptors can underlie the detection of a vast chemical world.