9UTC

The VFT domains of human sweet taste receptor TAS1R2 and TAS1R3 in the sucralose-bound state

Summary for 9UTC

• Entry DOI: 10.2210/pdb9utc/pdb
• EMDB information: 64488
• Related PRD ID: PRD_900090
• Descriptor: Taste receptor type 1 member 2,Taste receptor type 1 member 2,Engineered red fluorescent protein mScarlet3, Taste receptor type 1 member 3,mNeonGreen, 4-chloro-4-deoxy-alpha-D-galactopyranose-(1-2)-1,6-dichloro-1,6-dideoxy-beta-D-fructofuranose (3 entities in total)
• Functional Keywords: gpcr, taste receptor, tas1r2, tas1r3, sucralose, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 247495.46

Authors

Shi, Z.J.,Xu, W.X.,Yue, X.L.,Wu, L.J.,Hua, T.,Liu, Z.J. (deposition date: 2025-05-03, release date: 2025-07-16, Last modification date: 2025-10-01)

Primary citation

Shi, Z.,Xu, W.,Wu, L.,Yue, X.,Liu, S.,Ding, W.,Zhang, J.,Meng, B.,Zhao, L.,Liu, X.,Liu, J.,Liu, Z.J.,Hua, T.
Structural and functional characterization of human sweet taste receptor.
Nature, 645:801-808, 2025

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. ), 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.

PubMed: 40555359
DOI: 10.1038/s41586-025-09302-6

Experimental method

ELECTRON MICROSCOPY (3.33 Å)