NIAID Now | October 12, 2018
While humans rely strongly on sight and hearing to navigate their environment, for insects it’s all about odor. Butterflies, for example, find nectar-filled flowers by smell, while mosquitoes are pros at sniffing out people or other potential sources of the blood meals they require. The success of insects—the most diverse group of multicellular organisms on Earth—is linked to their ability to detect and distinguish an enormous variety of volatile chemicals in the environment, allowing them to thrive in a wide range of ecological niches. Now, new research by NIAID-supported scientists reveals how the shape of a key insect "sniffer" molecule makes this olfactory virtuosity possible.
To cope with an almost unlimited range of chemical odorants in the environment, insects have evolved a similarly enormous variety of odor receptors. Researchers estimate there are tens of millions of distinct receptors, each capable of detecting a different chemical. All the receptors function as ion channels; they create a tunnel that opens to a flow of charged ion particles when the receptor meets its target odor molecule. The ion channels are made up of two subunits, an odorant co-receptor (Orco)—which varies very little in amino acid sequence across the insect world—and an odorant receptor, which is the highly variable portion. Until recently, however, no visualization technologies were available to allow investigators to determine what the ion channels look like in action or determine how they allow different insects to distinguish different odors.
The advent of cyro-electron microscopy—a technique for analyzing proteins and other molecular features by beaming electrons at frozen samples—offered a way to see how odor receptors are structured. Using cryo-EM, a team at Rockefeller University led by NIAID grantee Dr. Vanessa Ruta focused its attention on the Orco found in a parasitic fig wasp. Analysis of the cryo-EM data allowed them to determine that the channel consists of a single central pore, through which the ions pass, surrounded by four subunits. The subunits are bound together very loosely at a single point, called the anchor domain. Aptly, the structure of the channel is reminiscent of a bunch of flowers, Dr. Ruta noted in a Rockefeller University news story about the finding. “It’s almost like a bouquet with each flower held together at the center and the stalks splaying apart in different directions,” she said.
Ultimately, Dr. Ruta added, knowledge about the shape of Orco may allow scientists to develop better ways to interfere with insects’ ability to smell and feed on people. “We hope to take advantage of our structural insights to develop better repellents and help relieve the human health burden associated with malaria and other mosquito-borne diseases,” she said.
JA Butterwick et al. Cryo-EM structure of the insect olfactory receptor Orco. Nature DOI: 10.1038/s41586-018-0420-8 (2018).