To progress in the understanding of olfaction, visualizing the connection of the odorant with the olfactory receptors remains a challenge.
By solving the structure of olfactory receptors, a Franco-American team of scientists was able to show how they bind to odorant molecules and what are the associated activation mechanisms*. Results published in the journal Nature which could find applications in perfumery and the food industry, but also inpharmaceutical industry.
Our sense of smell relies on the interaction between the odor molecules we inhale and proteins called “olfactory receptors”. These receptors have long been black boxes whose three-dimensional structure at the atomic scale was unknown to us. However, to progress in understanding olfaction, visualize the way in which molecule odorant binds to the receptor is an essential step. In 2023, the very first structure of a human olfactory receptor was published in Nature. It was that of a class I receptor, a class which represents 16% of our receptors specialized in the detection of carboxylic acids**.
The structure of class II olfactory receptors, which represent 84% of our receptors and which we use to smell almost all of the odor molecules that we detect, remained unknown until today. For a very simple reason: in humans or other mammals, these receptors are not expressed (produced) in sufficient quantities to allow the elucidation of their structure. This low expression has long prevented the structural determination of olfactory receptors, which has made their study particularly difficult until today.
To get around this difficulty, scientists from the Institute of Chemistry of Natural Substances (CNRS) and Duke University have constructed sequences*** of olfactory receptors called “consensus” from theensemble sequences of a subfamily of olfactory receptors present in our nez.
To do this, they selected, for each of the 350 positions, the amino acid most frequently observed in all the receptors of this subfamily. Produced in sufficient quantity, these consensus receptors, “models” of a family of olfactory receptors, allowed them to obtain four new experimental structures of olfactory receptors including three structures of class II receptors linked to various odorant molecules.
These structures reveal that class I and class II olfactory receptors use distinct odorant molecule binding modes and different activation mechanisms. Class I receptors use a simple activation mechanism. A single amino acid, present in all receptors of this class, is involved in the detection of carboxylic acids.
On the other hand, class II receptors which bind to much more varied molecules require several amino acids, distributed throughout their cavity, to detect these different odorant molecules.
Results which will have an impact on our understanding of the perception of odors and which will find applications in the fields of perfumery and the food industry. But not only that. They could also be of interest to pharmacologists because some of these olfactory receptors are expressed in many cell types outside of our olfactory system and appear to play a role in the proliferation of several cancers.
Notes:
*An olfactory receptor-associated activation mechanism describes the process by which an odorant molecule binds to an olfactory receptor, triggering a cascade of reactions within the sensory neuron that results in the perception of an odor.
**Carboxylic acids are R-COOH groups found in cheese, coconut, certain fruits, vinegar and many animal or vegetable oils.
*** Each olfactory receptor is made up of a sequence of approximately 350 amino acids.
Editor: CCdM
Reference:
Engineered odorant receptors illuminate the basis of odour discrimination
Nature 2024 – https://www.nature.com/articles/s41586-024-08126-0
DOI: 10.1038/s41586-024-08126-0.
