Orco is the co-receptor of insect odorant receptors (ORs), expressed in olfactory sensory neurons (OSNs). Its structure and function are highly conserved across insect species.
Function
Orco is essential for the function and membrane localization of ORs. This co-receptor binds to a specific odorant receptor (ORx) on the membrane of OSNs, forming a heteromeric complex. Thus, the ORx/Orco complex functions as a non-selective cation channel, with ORx ensuring the specificity of odor and pheromones ligands that activate the channel, contributing to signal transduction which results in behavioral changes. In the absence of an ORx, Orco is also capable of forming functional channels activated by VUAA1.
Structural highlights
In the absence of an ORx, Orco is capable of forming a homotetramer, with four subunits encircling a channel. Each subunit is composed of 7 transmembrane helices (S1-S7), an intracellular N-terminal, and an extracellular C-terminal. The majority of the protein is intramembranous, while small loops are exposed to the extracellular environment, and a small intracellular domain, called the anchor domain, extends into the cytoplasm. The anchor domain is named as such for establishing the majority of interactions between subunits and thus 'anchoring' each of them within the lipid membrane. The S1-S6 domains of each subunit are linked to their respective S7b helix and are 7 Å apart from the domains of the other subunits. Each subunit contributes a S7b helix that aligns the central pore for ion passage. This pore presents a narrow passage at its extracellular end, where two residues, Leu 473 and Val 469, are separated by only 2 Å, preventing the passage of hydrated ions, characterizing its closed state.
