According to the National Institutes of Health, the human nose can distinguish over 1 trillion scents. Our sense of smell enables us to explore a diverse range of odor molecules, yet it is also the least well-understood among all our senses.

Decoding the Works of Smell Receptors: Scientists Determine How Scent Molecules are Captured
(Photo : Pexels/ Andrea Piacquadio)

Regardless of the source, every scent begins with odor molecules floating freely and attaching to the receptors in the nose. Such union in great numbers produces the human perception of smells that we either love or hate. For many years, scientists have attempted to investigate the mechanism of smell sensors in detecting and responding to odor molecules, but they failed to visualize it in granular detail.

 

Revealing the Secrets of the Smell Receptors

A team of researchers conducted a study focusing on the mechanism of how the specialized sensor proteins called smell receptors recognize and bind with the odorants. They were led by Hiroaki Matsunami, a neuroscientist and molecular geneticist investigating the senses of smell and taste at Duke University.

The olfactory receptors in humans belong to a family of proteins called G-protein-coupled receptors (GPCRs). Over the past two decades, researchers have successfully determined the structures of GPCRs, but not the olfactory receptors among them. This is because these receptors only mature in olfactory neurons and not in cultured cells in the laboratory.

To address this issue, Matsunami and his colleagues tried genetically altering the olfactory receptors to make them grow in cultured cells. To make this possible, the scientists used cryo-electron microscopy to determine the structure of OR51E2. This active receptor is known for its ability to bind with volatile fatty acid propionate.

The imaging technique allows them to generate detailed images of OR51E2 interlocked with the propionate, which triggers the sensory neuron. For the first time, they provided a molecular view of how the olfactory receptor captures the scent molecules in the air.

The team also found out that inside the intertwined molecules, the propionate was confined within a small pocket. This suggests that the highly changing loop contributes to our ability to detect varied scents. The reported three-dimensional structure of the receptor represents a breakthrough in understanding how the nose and the brain draw out sensations from airborne chemicals.

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Effect of Genetic Variations on Smell Receptors

Humans have almost 400 different types of olfactory receptors in their noses. One odor molecule can activate Several other olfactory receptors, while any given receptor can activate several different odor molecules.

A 2019 study at the Monell Chemical Senses Center sheds insight into the extensive individual differences in sensing odors. The research team found that small differences in olfactory receptor genes can impact how each receptor functions. Moreover, a change in a single receptor can be enough to affect the odor perception of a person.

This means that when two individuals smell the same molecule, one person may detect a particular color while the other interprets it another way. The result of this experiment also broadens experts' understanding regarding the ability of olfactory receptors in the nose to encode information about smell properties even before it reaches the brain.

 

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