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TitleStructural and functional characterization of human sweet taste receptor.
Journal, issue, pagesNature, Vol. 645, Issue 8081, Page 801-808, Year 2025
Publish dateJun 24, 2025
AuthorsZongjun 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 AbstractSweet 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 linksNature / PubMed:40555359
MethodsEM (single particle)
Resolution3.18 - 3.77 Å
Structure data

EMDB-64484, PDB-9ut8:
The full-length human sweet taste receptor TAS1R2 and TAS1R3 in the apo state
Method: EM (single particle) / Resolution: 3.41 Å

EMDB-64485, PDB-9ut9:
The VFT domains of human sweet taste receptor TAS1R2 and TAS1R3 in the apo state
Method: EM (single particle) / Resolution: 3.18 Å

EMDB-64486, PDB-9uta:
The transmembrane domains of human sweet taste receptor TAS1R2 and TAS1R3 in the apo state
Method: EM (single particle) / Resolution: 3.77 Å

EMDB-64487, PDB-9utb:
The full-length human sweet taste receptor TAS1R2 and TAS1R3 in the sucralose-bound state
Method: EM (single particle) / Resolution: 3.59 Å

EMDB-64488, PDB-9utc:
The VFT domains of human sweet taste receptor TAS1R2 and TAS1R3 in the sucralose-bound state
Method: EM (single particle) / Resolution: 3.33 Å

Source
  • homo sapiens (human)
  • discosoma sp. (sea anemone) (sea anemone)
  • branchiostoma lanceolatum (amphioxus)
  • discosoma sp. (sea anemone)
KeywordsSIGNALING PROTEIN / GPCR / Taste / Tas1R2 / Tas1R3 / Taste receptor / Sucralose

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