Cryo-EM structure of the insect olfactory receptor Orco.

Abstract

SummaryThe olfactory system must recognize and discriminate among highly diverse chemicals in the environment. To contend with such diversity, insects have evolved a unique family of odorant-gated ion channels composed of a highly conserved co-receptor (Orco) and a divergent odorant receptor (OR) that confers chemical specificity. Here, we present the single-particle cryo-electron microscopy structure of an Orco homomer at 3.5 Å resolution, providing the first structural insight into this receptor family. Orco possesses a novel channel architecture, with four subunits symmetrically arranged around a central pore that diverges into four lateral conduits that open to the cytosol. The Orco tetramer has few inter-subunit interactions within the membrane and is bound together by a small cytoplasmic anchor domain. The minimal sequence conservation among ORs maps largely to the pore and anchor domain, suggesting how the unique architecture of this receptor family accommodates their remarkable sequence diversity and facilitates the evolution of odour tuning.