Researchers led by Professor Naomi Osakabe at Shibaura Institute of Technology utilized the latest AI model, AlphaFold3 (AF3), to predict the detailed 3D structures of all 25 human bitter taste receptors (T2Rs), marking a significant advance in receptor structural biology.

Using AlphaFold3, scientists have achieved highly accurate structural predictions of T2Rs, which are crucial for taste perception and gut-brain communication, overcoming previous limitations in structural data.

The study compared AF3 predictions with earlier AlphaFold2 results and experimental structures, finding AF3 provided more precise models, especially for T2R14 and T2R46, which had previously only been structurally characterized via cryo-electron microscopy.

AF3 consistently outperformed previous models in accuracy, addressing past challenges in resolving T2R structures and enabling better understanding of receptor functions.

T2Rs are expressed not only in oral tissues but also in gastrointestinal neuropod cells, where they influence gut-brain axis regulation, glucose tolerance, and appetite control, with implications for metabolic diseases like diabetes.

The research highlights the role of T2Rs beyond taste perception, particularly in the gastrointestinal tract, where they help regulate glucose homeostasis and appetite, offering potential targets for health research.

Structural modeling of T2Rs is vital for understanding receptor functions and could inform future research on taste perception variability and receptor-ligand interactions.

Analysis of T2R structures revealed conserved intracellular regions responsible for signal transduction and highly variable extracellular regions involved in ligand recognition, which explains their broad specificity.

Researchers classified T2Rs into three clusters based on structural similarities and differences, aiding in understanding their specific functions and responses to bitter compounds.

Structural predictions suggest that diverse bitter compounds bind within the extracellular pockets of T2Rs, activating G proteins like -gustducin to trigger intracellular signaling pathways.

The structure of T2Rs enables recognition of a wide array of bitter compounds through interactions with specific G proteins, notably -gustducin.

Published in July 2025, this study exemplifies how AI and molecular biology integration deepens understanding of taste receptors and their broader physiological roles, with potential health implications.