We know when something tastes sweet but how does your brain actually get the message?
A new study from St. Jude Children’s Research Hospital offers a surprising glimpse inside your taste buds. Using advanced imaging, researchers have mapped out how sweeteners like sucralose activate the body’s sweet taste receptor, revealing a newly discovered “loose” state that sends the signal for sweetness. The findings, published in Cell Research, could help guide the design of better, safer sugar substitutes in the future.
At the heart of the discovery is a protein complex on your tongue made up of two parts: TAS1R2 and TAS1R3. When you eat something sugary, or sugar-like, these proteins shift their shape to tell your brain this is sweet.
The research team captured what that shape-shift actually looks like. They found that when a sweetener binds to one part of the receptor, it triggers the two proteins to loosen and separate, like a latch springing open.
“In this new structure, when the sweetener binds to TAS1R2, a loop of TAS1R2 inserts into the interface between TAS1R2 and TAS2R3, triggering the separation of VFT domains,” said Haolan Wang, PhD, one of the study’s co-first authors.
This change, the researchers say, is what flips the sweetness signal to “on.”
Their work focused on two common sugar substitutes: sucralose and advantame. While both triggered the same overall response, they interacted with the receptor in slightly different ways, offering valuable clues for designing future sweeteners that taste better, work more efficiently or require lower doses.
“Our structural and functional studies suggest that this ‘loose’ state, as we have dubbed it, is the fully activated state,” said corresponding author Chia-Hsueh Lee, PhD.
That finding may help explain how the sweet receptor can recognize so many different kinds of sweeteners.
“We were very curious about why this sweet taste receptor can bind to so many different kinds of sweeteners,” said Xiao Chen, PhD, another co-first author. “By revealing unprecedented snapshots of the sweet taste receptor, our study provides new insights into how we perceive sweetness and helps guide the design of better sweeteners.”
The discovery doesn’t change what’s on your plate today, but it may help shape the sweeteners of tomorrow. And for people managing sugar intake due to diabetes, metabolic health or personal choice, that could make the search for satisfying options a little bit sweeter.
This research was supported by the National Institutes of Health and ALSAC, the fundraising organization of St. Jude Children’s Research Hospital.