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| Title | Structural and functional characterization of human sweet taste receptor. |
|---|---|
| Journal, issue, pages | Nature, Vol. 645, Issue 8081, Page 801-808, Year 2025 |
| Publish date | Jun 24, 2025 |
Authors | 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 / Tian Hua / ![]() |
| PubMed 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. ), ...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. ), 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. |
External links | Nature / PubMed:40555359 |
| Methods | EM (single particle) |
| Resolution | 3.18 - 3.77 Å |
| Structure data | EMDB-64484, PDB-9ut8: EMDB-64485, PDB-9ut9: EMDB-64486, PDB-9uta: EMDB-64487, PDB-9utb: EMDB-64488, PDB-9utc: |
| Source |
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Keywords | SIGNALING PROTEIN / GPCR / Taste / Tas1R2 / Tas1R3 / Taste receptor / Sucralose |
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homo sapiens (human)
discosoma sp. (sea anemone) (sea anemone)
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