Structural and functional characterization of human sweet taste receptor

Zongjun Shi, Weixiu Xu, Lijie Wu, Xiaolei Yue, Shenhui Liu, Wei Ding, Jinyi Zhang, Bing Meng, Lianghao Zhao, Xiaoyan Liu, Junlin Liu, Zhi-Jie Liu () and Tian Hua ()
Additional contact information
Zongjun Shi: ShanghaiTech University
Weixiu Xu: ShanghaiTech University
Lijie Wu: ShanghaiTech University
Xiaolei Yue: ShanghaiTech University
Shenhui Liu: ShanghaiTech University
Wei Ding: Chinese Academy of Sciences
Jinyi Zhang: ShanghaiTech University
Bing Meng: ShanghaiTech University
Lianghao Zhao: ShanghaiTech University
Xiaoyan Liu: ShanghaiTech University
Junlin Liu: ShanghaiTech University
Zhi-Jie Liu: ShanghaiTech University
Tian Hua: ShanghaiTech University

Nature, 2025, vol. 645, issue 8081, 801-808

Abstract: 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 and TAS1R3 (refs. 1,2), senses a wide range of sweet compounds—including natural sugars, artificial sweeteners and sweet proteins—and affects metabolic regulation beyond taste. However, the lack of three-dimensional structures hinders our understanding of its precise working mechanism. Here we present cryo-electron microscopy 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 sweetener-recognition modes in TAS1R2. Structural comparisons further uncover conformational changes upon ligand binding and a unique activation mechanism. These findings illuminate the signal transduction mechanisms of chemosensory receptors in the class C GPCR family and provide the molecular basis for the design of a new generation of sweeteners.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-025-09302-6 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:645:y:2025:i:8081:d:10.1038_s41586-025-09302-6

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-025-09302-6

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().