Juen Zhang, Lu Zhengyuan, Yu Ruihuan, Chang Andrew N, Wang Brian, Fitzpatrick Anthony W P, Zuker Charles S
Zuckerman Mind Brain Behavior Institute and Department of Biochemistry and Molecular Biophysics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Howard Hughes Medical Institute, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Zuckerman Mind Brain Behavior Institute and Department of Biochemistry and Molecular Biophysics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Howard Hughes Medical Institute, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Biological Sciences, Columbia University, New York, NY, USA.
Cell. 2025 Jul 24;188(15):4141-4153.e18. doi: 10.1016/j.cell.2025.04.021. Epub 2025 May 7.
In humans, 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 chemicals. 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 describe the cryo-electron microscopy (cryo-EM) structure 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 such a wide range of sweet-tasting compounds, and open up unique possibilities for designing a generation of taste modulators informed by the structure of the human receptor.
在人类中，甜味的检测以及最终的感知始于口腔，在口腔中，专门负责甜味感知的味觉受体细胞（TRCs）会与糖类、人工甜味剂及其他甜味化学物质相互作用。人类甜味TRCs在其细胞表面表达一种甜味受体，该受体启动一系列信号事件，使我们对甜味刺激产生强烈的吸引力。在此，我们描述了与两种使用最广泛的人工甜味剂——三氯蔗糖和阿斯巴甜结合的人类甜味受体的冷冻电子显微镜（cryo-EM）结构。我们的研究结果揭示了甜味检测的结构基础，深入了解了单一受体如何介导我们对如此广泛的甜味化合物的所有反应，并为基于人类受体结构设计新一代味觉调节剂开辟了独特的可能性。
