Scientists at St. Jude Children’s Research Hospital have made significant strides in understanding how human sweet receptors detect sugar and other sweeteners. As a result of their pioneering research, they discovered a new way we detect sweetness. It provides new structural understanding into the structural dynamics of these receptors that mediate this fascinating sensation. Those results, which form part of a detailed biochemical study published in the journal Cell Research, uncovered an unexpected activation mechanism.
The sweet taste receptor belongs to a protein family that includes the class C GPCRs. Specifically, it comprises two proteins: TAS1R2 and TAS1R3. Sweet taste receptors reside in the mouth’s taste buds. They’re particularly important for loading on to and recognizing various sweet materials like sugars, artificial sweeteners, etc. The precise mechanism by which these special receptors trigger a sweet response has not been completely understood until this new study.
A Closer Look at the Sweet Receptor
Research team members combined advanced structural biology methods to visualize the sweet taste receptor. They used cryo-electron microscopy to freeze the receptor in different conformational states as it interacts with the range of potential sweeteners. This groundbreaking effort enabled researchers to catch the receptor in action, especially when it comes to its interactions with sucralose and advantame.
Haolan Wang, Ph.D., with colleague Xiao Chen, both of the St. Jude Department of Structural Biology, directed the overall investigation. Crucially, their work provided an unprecedented view into what they termed the “loose” state of the receptor. This state corresponds to the characteristic flower shape produced by the extensible part of the Venus flytrap (VFT) domain of TAS1R2 and TAS1R3. This floppy state seems to be key to getting the sweet taste receptor into its active form.
“In this new structure, when the sweetener binds to TAS1R2, a loop of TAS1R2 inserts into the interface between TAS1R2 and TAS1R3, triggering the separation of VFT domains,” – Haolan Wang.
Understanding the Mechanism of Activation
The research results point to important new understandings of what makes the sweet taste receptor tick. It undergoes a dramatic folding transformation when it’s complexed with a sugar molecule. This change in conformation, called a “lock and key” mechanism, is essential for triggering the sweet taste response. The discovery of this unbound state represents an important step towards understanding how these receptors are able to bind such a wide range of sweeteners.
Chia-Hsueh Lee, a senior researcher who worked on the study, said that their findings could not be more timely. “There’s a lot of functional data accumulated in the literature, but without capturing the receptor’s full range of motion, it’s tough to understand the molecular mechanism,” he explained. The results of the study indicate that this loose state may be the completely activated state of the receptor.
“Our structural and functional studies suggest that this ‘loose’ state, as we have dubbed it, is the fully activated state,” – Chia-Hsueh Lee.
These findings might help to identify and design even sweeter compounds. Lee noted that with this newfound knowledge of receptor activation mechanisms, researchers can infer that molecules stabilizing this particular loose state should exhibit increased sweetness.
“We were very curious about why this sweet taste receptor can bind to so many different kinds of sweeteners,” – Xiao Chen.
Implications for Future Research
The impact of this research goes far beyond our interest in understanding taste perception. Understanding how sweet taste receptors function could lead to advancements in food science and nutrition, particularly in developing new sweeteners and enhancing existing ones.
This study opens up some intriguing avenues for future research. In this way, it looks at how these receptors may respond to various flavors and tastes, deepening our scientific appreciation of sensory biology. The team’s work contributes greatly to scientific understanding. It holds promise for use in a number of practical applications for various sectors, such as food and pharma.