2026 Theses Doctoral

Structural Basis of Human Sweet Taste

Lu, Zhengyuan

The taste of sweet is one of the most iconic and culturally universal human sensory experiences. It produces appetitive responses in humans and animals, drives the ingestion of energy-rich food sources, and promotes a diet that includes critical macronutrients. In humans, it also evokes a sense of pleasure, satisfaction, and comfort. The detection and ultimately the perception of sweetness begin in the oral cavity, where taste receptor cells (TRCs) dedicated to sweet-sensing interact with sugars, artificial sweeteners, and other sweet-tasting substances.

Human sweet TRCs express on their cell surface a sweet receptor that initiates the cascade of signaling events responsible for our strong attraction to sweet stimuli. Here, we present the cryo-electron microscopy (cryo-EM) structures of the human sweet receptor bound to two of the most widely used artificial sweeteners—sucralose and aspartame. Our results reveal the structural basis for sweet detection, provide insights into how a single receptor mediates all our responses to a wide range of sweet-tasting compounds, and open up novel possibilities to design a new generation of taste modulators informed by the structure of the human receptor.