How a Human Smell Receptor Works Is Finally Revealed

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How a Human Smell Receptor Works Is Finally Revealed

After decades of frustration, researchers have determined how an airborne scent molecule links to a human smell receptor.

Wynne Parry,  Contributing Writer, May 1, 2023  in Quantamagazine.

For the first time, researchers have determined how a human olfactory receptor captures an airborne scent molecule, the pivotal chemical event that triggers our sense of smell.

Whether it evokes roses or vanilla, cigarettes or gasoline, every scent starts with free-floating odor molecules that latch onto receptors in the nose. Multitudes of such unions produce the perception of the smells we love, loathe or tolerate. Researchers therefore want to know in granular detail how smell sensors detect and respond to odor molecules. Yet human smell receptors have resisted attempts to visualize how they work in detail — until now.

In a recent paper published in Nature, a team of researchers delineated the elusive three-dimensional structure of one of these receptors in the act of holding its quarry, a compound that contributes to the aroma of Swiss cheese and body odor.

“People have been puzzled about the actual structure of olfactory receptors for decades,” said Michael Schmuker, who uses chemical informatics to study olfaction at the University of Hertfordshire in England. Schmuker was not involved in the study, which he describes as “a real breakthrough.”

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He and others who study our sense of smell say that the reported structure represents a step toward better understanding how the nose and brain jointly wring from airborne chemicals the sensations that warn of rotten food, evoke childhood memories, help us find mates and serve other crucial functions.

The complexity of the chemistry that the nose detects has made olfaction particularly difficult to explain. Researchers think that human noses possess about 400 types of olfactory receptors, which are tasked with detecting a vastly larger number of odoriferous “volatiles,” molecules that vaporize readily, from the three-atom, rotten-egg-smelling hydrogen sulfide to the much larger, musky-scented muscone. (One recent estimate put the number of possible odor-bearing compounds at 40 billion or more.)

“In my mind, one of the most amazing things about olfaction is our ability to detect and discriminate such a wide array of volatiles,” said Hiroaki Matsunami, an olfaction researcher at Duke University and an author of the new study.

Caught in the Act

Perched on the surface of neurons in the nose, olfactory receptors change shape when they snag odor molecules. This reconfiguration prompts the neurons to send signals to the odor-processing parts of the brain. Researchers have long sought to see in detail how the interaction between receptor and odor molecule plays out. .... '