First 3D Structure of Human Odor Receptor

Have you ever wondered how your nose is able to detect different scents? The answer lies in proteins in your nose called olfactory receptors. These receptors are responsible for detecting molecules and translating them into scents. However, little is known about exactly how these receptors recognize specific odorants and encode different smells in the brain. That is, until now.

In a study published in Nature on March 15, researchers have mapped the precise 3D structure of a human odor receptor for the first time, taking a step forward in understanding the most enigmatic of our senses. The study describes an olfactory receptor called OR51E2 and shows how it ‘recognizes’ the smell of cheese through specific molecular interactions that switch the receptor on.

The human genome contains genes encoding 400 olfactory receptors that can detect many odors. Each olfactory receptor can interact with only a subset of smelly molecules called odorants, and a single odorant can activate multiple receptors. This means that it is like hitting a chord on a piano, where a combination of keys gives rise to the perception of a distinct odor.

Technical challenges in producing mammalian olfactory-receptor proteins using standard laboratory methods have made it difficult to study how these receptors bind to odorants. To overcome this, the researchers focused on the OR51E2 receptor, which has functions beyond odorant recognition and is found in gut, kidney, and prostate tissues, as well as olfactory neurons.

OR51E2 interacts with two odorant molecules: acetate, which smells like vinegar, and propionate, which has a cheesy odor. The authors isolated the receptor and analyzed the structure of propionate-bound and unbound OR51E2 using cryo-electron microscopy, an atomic-resolution imaging technique. They also used computer-aided simulations to model how the protein interacts with the odorant at an atomic scale.

They found that propionate binds OR51E2 through specific ionic and hydrogen bonds that anchor the propionate’s carboxylic acid to an amino acid, arginine, in a region of the receptor called the binding pocket. Binding to propionate alters the shape of OR51E2, which is what turns the receptor on. These molecular interactions are crucial, as the researchers showed that mutations affecting arginine prevented OR51E2 from being activated by propionate.

The OR51E2 receptor is specific to propionate and acetate. However, studying other examples of human odor receptors and elucidating their structures is crucial, as it will allow for a broader understanding of the different ways that odorants are recognized. Scientists have long dreamed of building a molecular atlas of olfactory receptors that maps their chemical structures and which combinations of receptors correspond to particular odors. The findings from this study bring us one step closer to this dream.

This breakthrough in mapping the 3D structure of a human odour receptor is an exciting development in the field of olfactory research. It sheds light on the mechanisms behind how we detect specific odours and could lead to a greater understanding of how our sense of smell works.

One potential application of this research is in the development of new fragrances and flavours. By understanding how certain odour receptors interact with specific molecules, scientists may be able to design new scents and tastes that are more targeted and effective.

Another potential benefit of this research is in the development of new medical treatments. The OR51E2 receptor, which was the focus of this study, is found not only in the nose but also in other parts of the body such as the gut and kidney. By understanding how this receptor works, researchers may be able to develop new therapies for conditions that affect these organs.

However, it is important to note that this is just the first step in a long journey towards a comprehensive understanding of the human sense of smell. There are still many unanswered questions about how our olfactory system works, such as why we find certain smells pleasant and others repulsive, and how we are able to distinguish between similar smells.

Nevertheless, this study is a significant step forward in our understanding of the human sense of smell, and it opens up new avenues for research that could have a wide range of practical applications.