Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments

• DOI: 10.1038/s42004-024-01324-x
• Publication Date: 2024-10-18T17:02:31Z
• Authors: Shuang Hao; Brian Guthrie; Soo-Kyung Kim; Sergej Balanda; Jan Kubicek; Babar Murtaza; Naim A. Khan; Pouyan Khakbaz; Judith Su; William A. Goddard
• Keywords: Sweet Taste; Taste receptor; Steviol

Sucrose provides both sweetness and energy by binding to Venus flytrap domains (VFD) of the heterodimeric sweet taste receptor (T1R2/T1R3). In contrast, non-caloric sweeteners such as sucralose aspartame only bind one specific domain (VFD2) T1R2, resulting in high-intensity sweetness. this study, we investigate mechanism various steviol glycosides, artificial sweeteners, a negative allosteric modulator (lactisole) at four distinct sites: VFD2, VFD3, transmembrane 2 (TMD2), TMD3 through experiments computational docking studies. Our results reveal multiple sites for tested ligands, including radiolabeled ligands. experimental evidence demonstrates that C20 carboxy terminus Gα protein can intracellular region either TMD2 or TMD3, altering GPCR affinity high-affinity state glycosides. These findings provide mechanistic understanding structure function receptor. other different (T1R2/T1R3), levels Here, authors T1R2/T1R3 studies, revealing ligands structural– correlations ligand–receptor interactions.