The recent breakthrough by scientists at UC San Francisco in creating the first 3D picture of how an odor molecule activates a human odorant receptor has significant implications for multiple fields of study, particularly in fragrance and food science. For decades, researchers have struggled to map the interactions of thousands of scent molecules with hundreds of odorant receptors, allowing chemists to design a molecule and predict what it would smell like. This new understanding of olfaction can open the door to creating novel smells based on understanding how a chemical’s shape leads to a perceptual experience, much like how drugs are designed today based on the atomic shapes of disease-causing proteins.

Odorant receptors are proteins that bind odor molecules on the surface of olfactory cells and make up half of the largest and most diverse family of receptors in our bodies. The 3D picture of how an odor molecule activates a human odorant receptor is poised to reignite interest in the science of smell, paving the way for new insights into various biological processes. There are about 400 unique receptors involved in the sense of smell, and each of the hundreds of thousands of scents we can detect is made of a mixture of different odor molecules. Each type of molecule may be detected by an array of receptors, creating a puzzle for the brain to solve each time the nose catches a whiff of something new.

The image of how propionate, a molecule that contributes to the pungent smell of Swiss cheese, binds to the odorant receptor OR51E2 is an essential step in deciphering the sense of smell. This molecular snapshot showed propionate sticks tightly to OR51E2 thanks to a specific fit between odorant and receptor. The finding is consistent with one of the duties of the olfactory system as a sentinel for danger. While propionate contributes to the rich, nutty aroma of Swiss cheese, its scent is much less appetizing on its own. Receptors for pleasing smells like menthol or caraway might instead interact more loosely with odorants, according to Aashish Manglik, an associate professor of pharmaceutical chemistry and senior author of the study.

Researchers are now making better ways to study other odorant-receptor pairs and figure out how receptors are involved in things other than smell. For example, receptors have been linked to prostate cancer and the release of serotonin in the gut. The team thinks that in the future, new smells will be made by understanding how the shape of a chemical affects how it is perceived. This discovery is just the start, and it could be used for a lot more than just the perfume and food industries. It opens up exciting new possibilities for future scientific discoveries.

This new research was published in the journal Nature.

References

• Billesbølle, C. B., De March, C. A., Van Der Velden, W. J. C., Ma, N., Tewari, J., Del Torrent, C. L., Li, L., Faust, B., Vaidehi, N., Matsunami, H., & Manglik, A. (2023). Structural basis of odorant recognition by a human odorant receptor. Nature, 615(7953), 742–749. https://doi.org/10.1038/s41586-023-05798-y
• University of California San Francisco. (2023, March 15). Making Sense of Scents: First Molecular Images of Olfaction Open Door to Creating Novel Smells. University of California San Francisco; University of California San Francisco. https://www.ucsf.edu/news/2023/03/424956/making-sense-scents