Show Notes
️ Episode 17: The Structure of Human Sweetness — Cryo-EM of the TAS1R2+TAS1R3 Sweet Taste Receptor
In this episode of Base por Base, we explore a landmark cryo-electron microscopy study by Juen et al. (2025) published in Cell, which reveals the high-resolution structure of the human sweet taste receptor heterodimer TAS1R2+TAS1R3 bound to the artificial sweeteners sucralose and aspartame, providing the first detailed view of how a single receptor recognizes a diverse array of sweet compounds.
Highlights of the study: The TAS1R2 subunit binds sweet ligands while TAS1R3 remains in an open conformation; a common binding pocket accommodates both sucralose and aspartame via key conserved residues; site-directed mutagenesis confirms the functional importance of these residues for receptor activation; 3D variability analysis uncovers coordinated conformational changes between subunits; and structural analysis of the transmembrane and cysteine-rich domains illuminates the mechanism of G protein coupling exclusively through TAS1R2.
Conclusion: This work establishes a structural framework for designing novel taste modulators and deepens our understanding of sweet taste physiology, paving the way for targeted strategies in nutrition, health, and flavor engineering.
Reference: Juen, Z., Lu, Z., Yu, R., Chang, A. N., Wang, B., Fitzpatrick, A. W. P., & Zuker, C. S. (2025). The structure of human sweetness. Cell, 188, 1–13. https://doi.org/10.1016/j.cell.2025.04.021
License: This episode is based on an open access article published under the Creative Commons Attribution 4.0 International (CC BY 4.0) license – https://creativecommons.org/licenses/by/4.0/
