Cryo-EM structure of the insect olfactory receptor Orco

Abstract

The olfactory system must recognize and discriminate amongst an enormous variety of chemicals in the environment. To contend with such diversity, insects have evolved a family of odorant-gated ion channels comprised 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 from the parasitic fig wasp Apocrypta bakeri at 3.5 Å resolution, providing 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, shedding light on how the architecture of this receptor family accommodates its remarkable sequence diversity and facilitates the evolution of odour tuning.

Putative ligand binding sites of two functionally characterized bark beetle odorant receptors

“…This assumption is reasonable because ORs and Orco are believed to share a common ancestor 8 and because structural features of proteins generally are more conserved than their functions. Similar to the Orco structure 12 , our models of ItypOR46 and ItypOR49 revealed a cleft exposed to the extracellular side. Based on its location, it is reasonable to assume that this cleft is important for ligand binding, and this assumption is further supported by numerous studies of other ORs where mutations to residues lining this cleft have affected the responses (summarized in 44 ).…”

“…The ItypOR46 and ItypOR49 homology models were likewise converted to pdbqt format. As in the Orco structure 12 , an approximately 20 Å deep wedge-shaped cavity at the extra cellular side, formed by helices 2 to 6, was identified. Residues lining the cavity were defined as flexible and input pdbqt files for AutoDock Vina 1.1.2 ref70 were produced using ADT as well as a grid box for molecular docking simulation, covering the entirety of the putative binding cavity.…”

“…With few exceptions (reviewed in 9 ), a single OR gene is expressed in each OSN together with the co-receptor Orco, which is conserved across insects, except in the most basal taxa 11 . Together, the OR and Orco are suggested to form a heterotetrameric receptor complex 12 , with Orco being essential for the formation of an ion channel upon ligandinduced activation of the OR 13,14 . Current knowledge of the molecular and functional evolution of the ORs as well as the ligand-OR interaction is however limited, yet crucial for understanding insect chemical ecology and species-specific sensory adaptations.…”

The diversity and evolution of odorant receptors in beetles (Coleoptera)

“…The OR family evolved from a lineage of GRs (Robertson et al, 2003), and the few comprehensive functional analyses suggest that each receptor includes a unique ligand binding site that varies in its specificity (reviewed in Andersson et al, 2019). Together with the olfactory receptor coreceptor (Orco), these 'specific ORs' form a heterotetrameric receptor complex (Butterwick et al, 2018) in the membrane of olfactory sensory neurones. Orco exists as a single and highly conserved orthologue in each species, and it is necessary for the function of the receptor complex (Larsson et al, 2004;Vosshall and Hansson, 2011).…”

Transcriptome Surveys in Silverfish Suggest a Multistep Origin of the Insect Odorant Receptor Gene Family

“…At the molecular level, the functional Or signal transduction complex is a heteromultimer (most likely a heterotetramer) of a specific Or (Orx), which defines the ligand-specificity of the complex, and the ubiquitously expressed Orco (Butterwick et al, 2018;Dobritsa et al, 2003;Hallem et al, 2004;Hopf et al, 2015). Orco functions as a chaperone in intracellular Or trafficking and as an essential component of a non-selective cation channel that opens upon ligand-binding to the specific Orx leading to the depolarization and hence excitation of the sensory neuron expressing the Orx/Orco complex (Larsson et al, 2004;Sato et al, 2008;Wicher et al, 2008).…”