Bitterness receptors beyond the tongue

Researchers have uncovered the structure of a known, widespread human taste receptor, which may help scientists understand the role it plays outside the tongue. "What we found was totally unexpected," says Bryan Roth, one of the lead authors of the study published in Nature (2024, DOI: 10.1038/s41586-024-07253-y ). The orthosteric site on a receptor is typically the main site where a ligand would bind. This site is in contrast to the allosteric site , which is elsewhere on the receptor and plays more of a modulator role. The Roth team found that the receptor, TAS2R14, does not bind tastants at the orthosteric site, which is where they would be expected to bind. Instead, they found that cholesterol would bind to that orthosteric site. Cholesterol itself does not seem to activate TAS2R14, but it seems to "prime" the receptor so that the receptor can respond when a bitter tastant binds to