Scientists Map the 3D Structure of the Human Sweet Taste Receptor

For the first time, researchers have created a 3D map of the human sweet taste receptor. This breakthrough, achieved through cryo-electron microscopy, provides significant insights into how sweetness is perceived and our cravings for sugar. The detailed structure reveals the binding mechanism of sweeteners to a key component of the receptor called TAS1R2, which oddly resembles a Venus flytrap.

This discovery holds the potential to develop new molecules that might better control or lessen sugar cravings, which is crucial in the fight against obesity and diabetes. Unlike current artificial sweeteners that were stumbled upon accidentally and often fail to curb sugar cravings, this new understanding could pave the way for improved alternatives.

Key Facts:

• Structural Breakthrough: First high-resolution map (2.8 angstroms) of the human sweet taste receptor.
• Sweet Binding Pocket: Shows how substances like sucralose and aspartame attach to trigger sweetness.
• Potential Applications: May result in better sugar substitutes and insights into metabolic health.

Our affinity for sugar has become alarmingly excessive, with Americans consuming over 100 pounds annually, a significant increase from 18 pounds in 1800. This new research, published on May 7 in Cell, represents a vital advancement in addressing this pressing public health issue.

Mapping the 3D structure of the human sweet taste receptor could lead to new regulators that significantly affect our attraction and appetite for sugar.

“The impact of sugar on obesity is undeniable,” commented Juen Zhang, a postdoctoral fellow involved in the study. “Current artificial sweeteners don’t significantly alter our sugar cravings, but knowing the receptor’s structure might enable us to create something more effective.”

The sweet receptors in our mouths can detect various sweet chemicals, ranging from common table sugar to unique substances found in foods. Interestingly, these receptors aren’t particularly sensitive compared to those for other tastes, which makes our desire for sugar more pronounced and drives us to seek out sweet foods for energy.

Determining the receptor’s structure aids in understanding how it enables us to experience sweetness and can enhance our knowledge of taste perception. Over two decades ago, Dr. Zuker and his team identified the genes behind the mammalian sweet taste receptor, unveiling its chemical makeup. However, until now, its precise shape was unknown, much like recognizing a cake’s recipe without knowing how the finished product looks.

Without this structural knowledge, it has been challenging to explore how to rationally design ways to manage the function of this essential receptor. Most artificial sweeteners available today were either accidentally discovered or based on known sweet-tasting compounds, leading to various shortcomings.

The researchers devoted around three years using innovative methods to map the receptor’s structure, facing challenges in successfully growing the needed protein in lab conditions. “Obtaining the purified protein required over 150 different preparations,” explained Zhengyuan Lu, a doctoral student involved in the work.

Using cryo-electron microscopy, the team analyzed the structure of the sweet taste receptor by freezing the molecules in solution and firing electron beams to capture a range of snapshots, which helped in reconstructing its 3D shape at the atomic level. The binding pocket of the receptor is crucial, as it is where sweet substances attach to trigger the response driving our cravings.

“Accurate identification of this binding pocket is vital to comprehend its function,” noted study co-author Anthony Fitzpatrick, a principal investigator. By understanding its exact form, researchers can explore why certain sweeteners attach to it and how to design better molecules to activate or modulate the receptor’s function.

The sweet taste receptor has two main components, with TAS1R2 featuring the binding pocket that resembles a Venus flytrap. This structural knowledge might also explain individual differences in sweetness sensitivity. The team investigated the receptor’s configuration when linked with common artificial sweeteners like aspartame and sucralose, which are considerably sweeter than table sugar.

They systematically modified tiny sections of the receptor to better understand each part’s role in binding to sweeteners, with the goal of advancing scientific knowledge to assist people effectively. Although primarily found on taste buds, Dr. Zhang mentioned that this receptor is also present in various parts of the body, potentially influencing organ functions, such as those in the pancreas.

The implications of this new structural map of the sweet taste receptor extend to metabolic research and could be relevant in addressing disorders like diabetes.