Decoding the Mysteries of Human Olfaction

Human olfactory receptors (ORs), also known as odorant receptors, have a 3D structure that has recently been revealed by a ground-breaking investigation. Cryo-electron microscopy was a cutting-edge method employed in the research, which only recently came out in the esteemed scientific magazine Nature. This discovery could even result in further discoveries and has broad ramifications for a variety of biological systems.

Olfactory Receptors

Proteins called olfactory receptors (ORs), commonly referred to as odorant receptors, are in charge of detecting and relaying information about odors to the brain. With more than 400 distinct types thus far identified, the largest family of receptors in the human body includes odorant receptors. The odorant receptors are members of the G-protein coupled receptor (GPCR) family and are found in the olfactory epithelium, the portion of the nasal cavity that houses olfactory sensory neurons. GPCRs, otherwise known as heptahelical receptors or serpentine receptors, all have a tridimensional structure with seven transmembrane helices.

An electrical signal is produced in the olfactory receptor neuron when an odorant molecule attaches to an odorant receptor and sets off a chain reaction of physiological events. The olfactory bulb processes this signal before relaying it to higher brain areas for additional evaluation and interpretation.

Due to the extreme specificity of odorant receptor binding, each receptor only reacts to a certain subset of odorant molecules. Our capacity to perceive and distinguish between various odors depends on the sensitivity of odorant receptors.

Elucidating Mechanistic Activation

Our sense of smell depends heavily on odorant receptors, which constitute up half of the biggest and most diverse family of receptors in the human body. Because it paints a molecularly detailed, three-dimensional image of how an odor molecule triggers a human odorant receptor, the current work is remarkable. This is a critical step in understanding the sense of smell and could aid researchers in understanding how odor molecules attach to the appropriate olfactory receptors.

Power of Specificity

Cryo-electron microscopy was utilized in the study by researchers at the University of California, San Francisco (UCSF) to develop a 3D model of how an odor molecule triggers a human odorant receptor. They concentrated on the OR51E2 receptor, which is activated by propionate, a chemical involved in the strong Swiss cheese aroma. The study’s findings demonstrated that the propionate’s strong binding to OR51E2 is caused by a precise match between the odorant and receptor. This clarifies how our sense of smell can identify particular scents and even indicate when food has gone rotten, emphasizing the crucial function that our sense of smell plays in spotting potential threats.

Research Implications and Insights

The results of this study have broad implications. For instance, the fragrance business can make better-performing smells using this new information. Additionally, it may result in improved drug development, particularly for medicines that target the receptors responsible for taste and smell. A deeper comprehension of odorant receptors may pave the way for fresh biological investigations in various fields.

In this regard, the study on the structural underpinnings of odorant detection by a human OR reported in Nature offers hitherto unattainable insights into the molecular principles underlying the operation of the olfactory system. The results provide a fantastic starting point for further investigation into the complex operations of human ORs and could shed light on the riddles of smell perception.

Study DOI: 10.1038/s41586-023-05798-y

Engr. Dex Marco Tiu Guibelondo, BS Pharm, RPh, BS CpE

Editor-in-Chief, PharmaFEATURES