The secret functioning of olfactory receptors, finally revealed


The team’s observations may explain how insect scent receptors can typically evolve so quickly and diverge so much between species. Each insect species may have developed “its unique repertoire of receptors that are really well suited to its particular chemical niche,” said Ruta.

“This tells us there’s more going on than the idea of ​​receptors vaguely interacting with a bunch of ligands,” Datta said. A receptor built around a single binding pocket, with a response profile that can be readjusted by the smallest of settings, 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 the precise way in which olfactory receptors pick up so many different olfactory molecules.Photography: John D. and Catherine T. MacArthur Foundation

The architecture of the receiver also supported this view. Ruta and his colleagues found that they were four protein subunits loosely bound to the central pore of the canal, like the petals of a flower. Only the central region needed to be conserved as the receptor diversified and evolved; the genetic sequences governing the rest of the receptor units were less constrained. This structural organization meant that the receiver could adapt to a large degree of diversification.

Such mild evolutionary constraints at the receptor level probably impose substantial downstream selective pressure on neural circuits for olfaction: 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 make sense of them through learning and experience,” said Ruta.

Oddly, however, the nervous system doesn’t seem to ease the problem. Scientists had widely assumed that all receptors in an individual olfactory neuron were of the same class, and that neurons from different classes went to separate processing regions of the brain. In one pair of preprints posted last november, however, researchers have reported that in flies and mosquitoes, individual olfactory neurons express several classes of receptors. “Which is really surprising and would increase the diversity of sensory perception even more,” said Barber.

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

“This is the first olfactory recognition structure in any receptor of any species. But this is probably not the only mechanism of olfactory recognition, ”said Ruta. “This is only a solution to the problem. It would be very unlikely that this would be the only solution.

Despite this, she and other researchers believe there are many more general lessons to be learned from the jumping silk tail odor receptor. It’s tempting, for example, to imagine how this mechanism might apply to other receptors in the brains of animals – from those that detect neuromodulators like dopamine to those affected by various types of anesthetics – ” and how imprecise they are, “Barber said.” It offers a fascinating model for continuing to explore non-specific binding interactions. “

Perhaps this flexible and binding approach should also be considered in other contexts, she added. Published research in the Proceedings of the National Academy of Sciences in March, for example, suggested that even canonical lockable ion channel receptors might not be as strictly selective as scientists thought.

If many different types of proteins bind to receptors through flexible and weak interactions within a certain type of pocket, this principle could guide the rational design of drugs for various diseases, especially neurological disorders. At the very least, Ruta’s work on binding DEET to an insect scent receptor could provide information on how to develop targeted repellents. “The mosquito is still the deadliest animal on Earth” because of the diseases it carries, said Ruta.



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