Structure of the Insect Alkaline Taste Receptor Alka and Insights into Its Alkaline Ligand Recognition Mechanism

Taste perception governs dietary selection, with alkaline sensation playing a pivotal role in food avoidance. In <i>Drosophila</i>, a chloride channel named alkaliphile (Alka) is both necessary and sufficient for aversive taste responses to alkaline food. In this study, we resolved the high-resolution structure of Alka. Alka forms a homopentameric complex, with each subunit comprising four transmembrane helices. Residues P276, T280, and T284 were indicated as key regulators of channel gating. Guided by the structure, we performed molecular docking screening followed by surface plasmon resonance (SPR) validation, identifying three representative ligands that specifically interact with Alka. SPR analysis of Alka mutants confirmed that P276 is essential for ligand recognition, whereas T280 and T284 selectively affect ligand interactions. We also explored the binding dynamics between Alka and ligands. This study elucidates the molecular mechanisms underlying ligand binding and channel gating, providing a theoretical foundation for future studies on alkaline taste perception.