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)

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, 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-TAS1R3, 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.

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

Experimental method

ELECTRON MICROSCOPY (3.33 Å)