The secret action of odor receptors, finally revealed


The team’s observations may explain how insect olfactory receptors can generally develop so rapidly and diverge so much between species. Each insect species may have developed “its own unique repertoire of receptors that are really well suited to its particular chemical niche,” Ruth said.

“It tells us that more than the very idea of ​​receptors loosely communicating with a bunch of ligands is happening,” Datta said. A receptor built around a single binding pocket, with a responsive profile that can be adjusted to even the smallest of adjustments, could accelerate evolution by freeing it to explore a wide range of chemical repertoires.

Vanessa Ruta, a neuroscientist at Rockefeller University, turned to structural biology to gain new insight into how individual odor receptors sense so many different odor molecules.Photo: John D. and Catherine T. MacArthur Foundation

The receptor architecture also supports this view. Ruta and her colleagues found that it consisted of four protein subunits loosely connected to the central pore of the canal, like flower petals. Only the central region needed to be preserved as the receptor diversified and developed; the genetic sequences that control other receptor units were less restricted. This structural organization meant that the receptor could adapt to a wide degree of diversification.

Such evolutionary limitations of light at the receptor level are likely to impose considerable selective pressure downstream on neural circuits due to smell: Nervous systems need good mechanisms to decode disordered patterns of receptor activity. “Effectively, olfactory systems have evolved to take arbitrary patterns of receptor activation and give them meaning through learning and experience,” Ruta said.

It is intriguing, however, that the nervous system does not seem to alleviate the problem itself. Scientists have largely assumed that all receptors on an individual olfactory neuron are of the same class and that neurons of different classes go to separate areas of brain processing. U a couple of overprints published last Novemberhowever, researchers have reported that in both flies and mosquitoes, individual olfactory neurons express multiple classes of receptors. “Which is really surprising and which would further increase the diversity of sensory perception,” Barber said.

Rutin’s team’s findings are far from the last word on how olfactory receptors work. Insects use many other classes of olfactory ion channel receptors, including those that are much more complex and much more specific than those that jump. In mammals, the olfactory receptor is not even an ion channel; belongs to a completely different family of proteins.

“This is the first odorant recognition structure in any recipe of any kind. But that is probably not the only mechanism for recognizing uniforms, “Ruta said. “This is just one solution to the problem. It would be very unlikely that this was the only solution. ”

Nevertheless, she and other researchers think that many more general lessons can be learned from the olfactory receptor of popped bristles. It is tempting, for example, to imagine how this mechanism could be applied to other receptors in the animal’s brain – from those that detect neuromodulators such as dopamine to those affected by various types of anesthetics – is Barber. “It offers a fascinating model for continuing to explore nonspecific binding interactions.”

Perhaps this approach to flexible bonding should be considered in other contexts as well, she added. Published research u Proceedings of the National Academy of Sciences in March, for example, he suggested that even the canonical receptors for key ion channels may not be as strictly selective as scientists thought.

If many different types of proteins bind to receptors through flexible, weak interactions within some type of pocket, this principle could lead to the rational design of drugs for various diseases, especially neurological conditions. Routine work on binding DEET to the insect’s olfactory receptor could provide insight into how to develop targeted repellents. “The mosquito is still the deadliest animal on Earth” because of the disease it carries, Ruth said.

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