Hidden pocket in human bitter taste receptor discovered
New research has given insights into how we taste bitterness, revealing a hidden "pocket" inside a bitter taste receptor called TAS2R14. This could help us understand not only how we taste bitterness but also the roles these receptors play in other parts of the body.
Our bodies use 25 different receptors to detect bitter tastes, and many drugs can also activate these receptors. TAS2R14 is special because it can recognise and respond to a wide variety of bitter substances, including vitamins, certain drugs, and even some smells. However, until now, it was not fully understood how TAS2R14 binds to these substances and triggers a response.
Using advanced technology called cryo-EM, scientists were able to see the detailed structure of TAS2R14. They discovered that a bitter drug called flufenamic acid binds to TAS2R14 in two different places: one outside the cell and one inside. This dual binding helps explain how the receptor interacts with various compounds, including ones that cause bitterness.
Professor Masha Niv, Hebrew University of Jerusalem co-led the research and explained: “This discovery gives us a new clue into how TAS2R14 works. It’s fascinating because the receptor is not just sensing chemicals from outside the cell, like food or drugs, but also 'tasting' what’s happening inside the cell. This new intracellular pocket could be a game-changer in how we design drugs to interact with these receptors.”
Professor Peter McCormick, Department of Pharmacology and Therapeutics, University of Liverpool, carried out the receptor assays to understand how the two binding sites could be communicating. He commented: “The ability of this receptor to bind so many different molecules involved with taste suggest that these two sites may work together to recognise a wide range of "tastes" within the body. This discovery could lead to a better understanding of how we sense smells and taste.”
The paper ‘A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR’ was published in Nature Communications.