上海科技大学华甜课题组取得一项新突破。他们提出了人类甜味受体的结构与功能表征。相关论文发表在2025年6月24日出版的《自然》杂志上。

研究组在载脂蛋白和三氯蔗糖结合状态下展示了全长人类甜味受体的低温电镜结构。这些结构揭示了一种独特的不对称异二聚体结构，三氯蔗糖仅与TAS1R2的Venthem捕蝇器结构域结合。结合诱变和分子动力学模拟，本工作描绘了TAS1R2中的甜味剂识别模式。结构比较进一步揭示了配体结合后的构象变化和独特的激活机制。这些发现阐明了C类GPCR中化学感觉受体的信号转导机制，为新一代甜味剂的设计提供了分子基础。

据了解，甜味感知影响饮食选择和代谢健康。人类甜味受体是一种由TAS1R2-TAS1R3组成的C类G蛋白偶联受体（GPCR）异源二聚体，它能感知多种甜味化合物，包括天然糖、人工甜味剂和甜蛋白，影响味觉之外的代谢调节。然而，三维结构的缺乏阻碍了他们对其精确工作机制的理解。

附：英文原文

Title: Structural and functional characterization of human sweet taste receptor

Author: Shi, Zongjun, Xu, Weixiu, Wu, Lijie, Yue, Xiaolei, Liu, Shenhui, Ding, Wei, Zhang, Jinyi, Meng, Bing, Zhao, Lianghao, Liu, Xiaoyan, Liu, Junlin, Liu, Zhi-Jie, Hua, Tian

Issue&Volume: 2025-06-24

Abstract: Sweet taste perception influences dietary choices and metabolic health. The human sweet taste receptor, a class C G protein-coupled receptor (GPCR) heterodimer composed of TAS1R2-TAS1R31,2, senses a wide range of sweet compounds — including natural sugars, artificial sweeteners and sweet proteins — impacting metabolic regulation beyond taste. However, the lack of three-dimensional structures hinders our understanding of its precise working mechanism. Here, we present cryo-EM structures of the full-length human sweet taste receptor in apo- and sucralose-bound states. These structures reveal a distinct asymmetric heterodimer architecture, with sucralose binding exclusively to the Venus flytrap domain of TAS1R2. Combining mutagenesis and molecular dynamics simulations, this work delineates the sweeteners recognition modes in TAS1R2. Structural comparisons further uncover the conformational changes upon ligand binding and unique activation mechanism. These findings illuminate the signal transduction mechanisms of chemosensory receptors in class C GPCRs and provide molecular basis for new-generation sweetener design.

DOI: 10.1038/s41586-025-09302-6

Source: https://www.nature.com/articles/s41586-025-09302-6