Structure of Odor Recognition in Olfactory Receptors Observed

In a new study, a team of researchers from Rockefeller University has provided a molecular view of an olfactory receptor at work. The findings, published in Nature, reveal that olfactory receptors indeed follow a logic rarely seen in other receptors of the nervous system.

Using cryo-electron microscopy, the scientists found that while most receptors are precisely shaped to pair with only a few select molecules in a lock-and-key fashion, most olfactory receptors each bind to a large number of different molecules. Their promiscuity in pairing with a variety of odors allows each receptor to respond to many chemical components. From there, the brain can figure out the odor by considering the activation pattern of combinations of receptors.

“To form a basic understanding of odorant recognition we need to know how a single receptor can recognize multiple different chemicals, which is a key feature of how the olfactory system works and has been a mystery,” says researcher Josefina del Mármol. The team turned to the jumping bristletail, a ground-dwelling insect whose genome has been recently sequenced and has only five kinds of olfactory receptors. Although the jumping bristletail’s olfactory system is simple, its receptors belong to a large family of receptors with tens of millions of variants thought to exist in the hundreds of thousands of different insect species. The researchers chose OR5, a receptor from the jumping bristletail with broad recognition ability, responding to 60 percent of small molecules they tested.

They then examined OR5’s structure alone and also bound it to a chemical, either eugenol, a common odor molecule, or DEET, the insect repellent. “We learned a lot from comparing these three structures,” lead researcher Vanessa Ruta says. “One of the beautiful things you can see is that in the unbound structure the pore is closed, but in the structure where it’s bound with either eugenol or DEET, the pore has dilated and provides a pathway for ions to flow.”

The findings are likely representative of many olfactory receptors, Ruta says. “They point to key principles in odorant recognition, not only in insects’ receptors but also in receptors within our own noses that must also detect and discriminate against the rich chemical world.”