17: The structure of human sweetness

Juen Z et al., Cell - This episode examines a cryo-EM study that resolves the human sweet taste receptor (TAS1R2+TAS1R3) bound to two artificial sweeteners, revealing how a single receptor recognizes diverse sweet compounds and couples to G proteins. Key terms: sweet taste receptor, TAS1R2, TAS1R3, cryo-EM, sucralose. Study Highlights:Single-particle cryo-EM determined the structure of the human TAS1R2+TAS1R3 heterodimer bound to sucralose and aspartame at multi-angstrom resolution. The TAS1R2 subunit contains a conserved Venus flytrap (VFT) binding pocket that accommodates both sucralose and aspartame, while TAS1R3 remains in an open conformation. Site-directed mutagenesis of VFT residues (e.g., Y103, D142, S165, Y215, D278) altered ligand responses, supporting the mapped pocket. 3D variability analysis shows coordinated conformational changes between subunits and identifies elements linking ligand binding to the transmembrane and G protein-coupling regions. Conclusion:The cryo-EM structures define a common TAS1R2 binding pocket for high-potency sweeteners and reveal structural features linking agonist binding to G protein coupling, providing a foundation for structure-guided modulation of sweet taste. QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-05-13. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 7- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- The human sweet receptor TAS1R2+TAS1R3 forms an obligatory heterodimer mediating sweet detection.- There is a common binding pocket in TAS1R2 that binds both sucralose and aspartame.- TAS1R2 is the ligand-binding and G protein-coupling subunit; TAS1R3 anchors and maintains open conformation.- Key pocket residues Y103, D142, S165, Y215, D278 mediate ligand recognition; mutations disrupt function.- G protein coupling involves TAS1R2 residues Y756 and F827; mutations disrupt coupling.- TAS1R3 contributes to VFT dynamics and receptor activation; mutations in TAS1R3 affect function. QC result: Pass.