The secret action of olfactory receptors finally revealed

The team’s observations may explain how insects’ olfactory receptors can generally evolve so quickly and diverge so much between species. All kinds of insects may have evolved their “unique stock of receptors that really fit their own chemical niche,” Ruta said.

“It tells us there’s more going on than just the idea that receptors interact loosely with a set of ligands,” Datta said. A receiver built around a single binding pocket, with a response profile that can be reset with the smallest modifications, can accelerate development by freeing it up to explore a wide range of chemical munitions.

Vanessa Rota, a neuroscientist at Rockefeller University, has turned to structural biology to gain new insights into how individual olfactory receptors sense many different odor molecules.Photography: The John D. Foundation. and Catherine T MacArthur

The architecture of the future also supported this view. Rota and colleagues found that it consists of four protein subunits loosely bound at the central pores of the duct, like the petals of a flower. Only the central region needed to be preserved with the diversity and development of receptors; The genetic sequences governing the rest of the receptor units were less restricted. This structural organization means that the future can accommodate a wide degree of diversification.

Such mild evolutionary constraints at the receptor level would likely impose significant selective pressure downstream on neural circuits for olfaction: neural systems need good mechanisms to decode chaotic patterns of receptor activity. “Effectively, olfactory systems have evolved to take random patterns of receptor activation and give them meaning through learning and experience,” Ruta said.

Interestingly, however, the nervous system does not seem to make the problem any easier on themselves. Scientists have widely assumed that all the receptors on an individual olfactory neuron were of the same class, and that neurons of different classes go to separate processing areas in the brain. at A pair of preprints Posted last novemberHowever, the researchers reported that in both flies and mosquitoes, individual olfactory neurons express multiple classes of receptors. “This is really surprising, and it will increase the diversity of perception even more,” Barber said.

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

“This is the first structure for smell recognition in any receptor of any kind. But this is probably not the only mechanism for smell recognition,” Rutte said. “This is just one solution to the problem. It will be unlikely to be the only solution.”

However, she and other researchers believe there are many general lessons that can be learned from the jumping rough tail olfactory receptors. It’s tempting, for example, to imagine how this mechanism might apply to other receptors in animal brains—from those that detect neuromodulators like dopamine to those affected by different types of anaesthesia—”and how inaccurate it is to ‘let’ it,” Barber said. It provides a great model for further exploration of non-specific binding interactions.”

She added that perhaps this flexible binding approach should be considered in other contexts as well. Publish research In the Proceedings of the National Academy of Sciences In March, for example, he suggested that even canonical ionic lock-and-key channel receptors may not be as selective as scientists think.

If different types of proteins bind to receptors through weak, flexible interactions within a type of pocket, this principle could guide the rational design of drugs for various diseases, especially neurological conditions. At the very least, Rota’s work on binding DEET to insect olfactory receptors could provide insight into how to develop targeted repellents. “The mosquito is still the deadliest animal on Earth” because of the diseases it transmits, Rota said.

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