Episode 17

May 13, 2025

00:20:18

17: The structure of human sweetness

Hosted by

Gustavo B Barra
17: The structure of human sweetness
Base by Base
17: The structure of human sweetness

May 13 2025 | 00:20:18

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Show Notes

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.
Scope: article metadata and core scientific claims from the narration, excluding analogies, intro/outro, and music.
Factual QC score: 10/10.
Metadata QC score: 10/10.
Supported core claims: 7.
Claims flagged for review: 0.
Metadata checks passed: 4.
Metadata issues found: 0.
QC result: Pass.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
The structure of human sweetness

First author:
Juen Z

Journal:
Cell

DOI:
10.1016/j.cell.2025.04.021

Reference:
Juen Z., Lu Z., Yu R., Chang A.N., Wang B., Fitzpatrick A.W.P., Zuker C.S. The structure of human sweetness. Cell. 2025;188:1–13. doi: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 License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/structure-of-human-sweetness

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