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The secret work of olfactory receptors is finally revealed

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The team’s observations may explain how insect olfactory receptors usually evolve so rapidly, and the differences between species are so great. Ruta said that each insect species may have evolved “its unique receptor library, which is very suitable for its specific chemical niche.”

“It tells us that it’s not just the idea of ​​a receptor loosely interacting with a bunch of ligands,” Datta said. The response curve of a receptor built around a single binding pocket can be re-adjusted with minimal adjustments, and evolution can be accelerated by releasing it to explore an extensive chemical library.

Vanessa Ruta, a neuroscientist at Rockefeller University, turned to structural biology to gain new insights into how a single olfactory receptor accurately perceives so many different odor molecules.Photo: John D. and Catherine T. MacArthur Foundation

The receiver’s architecture also supports this view. Ruta and her colleagues discovered that it consists of four protein subunits, which are loosely bound in the central hole of the channel, like petals. With the diversification and evolution of receptors, only the central region needs to be conserved; the gene sequences that control the remaining receptor units are less restricted. This structural organization means that the receptor can adapt to a wide range of diversity.

This limitation of light evolution at the receptor level may impose tremendous selective pressure on the downstream neural circuits of the sense of smell: the nervous system needs a good mechanism to decode the chaotic patterns of receptor activity. “In fact, the olfactory system has evolved to adopt arbitrary receptor activation patterns and give them meaning through learning and experience,” Ruta said.

However, it is interesting that the nervous system does not seem to make the problem easier. Scientists generally believe that all receptors on a single olfactory neuron belong to the same category, and neurons of different categories travel to isolated processing areas of the brain.in a A pair of preprints Released in November last yearHowever, the researchers report that in flies and mosquitoes, individual olfactory neurons express multiple types of receptors. “This is really surprising and will further increase the diversity of sensory perception,” Barber said.

The findings of Ruta’s team are far from the final conclusion of how olfactory receptors work. Insects use many other classes of ion channel olfactory receptors, including those that are more complex and specific than jumping bristles. In mammals, olfactory receptors are not even ion channels. It belongs to a completely different protein family.

“This is the first structure for odor recognition in any receptor in any species. But this may not be the only mechanism for odor recognition,” Ruta said. “This is just one way to solve the problem. It is unlikely to be the only solution.”

Even so, she and other researchers believe that more general lessons can be learned from the olfactory receptors of jumping bristles. For example, it’s easy to imagine how this mechanism could be applied to other receptors in the animal’s brain—from receptors that detect neuromodulators such as dopamine to receptors that are affected by various anesthetics—”and how imprecise they are’allowed’. Yes,” Barber said. “It provides a fascinating model for continuing to explore non-specific binding interactions.”

She added that perhaps this flexible binding method should also be considered in other situations. Research publication inside Proceedings of the National Academy of Sciences For example, research in March showed that even classic key-lock ion channel receptors may not be as strictly selective as scientists believe.

If many different kinds of proteins bind to receptors through a certain type of flexible and weak interaction in the pocket, then this principle can guide the rational drug design for various diseases, especially neurological diseases. At least, Ruta’s work on DEET binding to insect olfactory receptors can provide insights on how to develop targeted insect repellents. “The mosquito is still the deadliest animal on the planet” because of the diseases it carries, Ruta said.

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