Sugars bind primarily to the extracellular 'Venus flytrap' domain of both T1R2 and T1R3, triggering a conformational change that activates the receptor.

The receptor's Venus flytrap domain acts like a clamshell that snaps shut upon sugar binding. This closure rearranges the receptor’s shape, especially in the transmembrane regions, which then activates internal signaling inside the taste cell. This molecular triggering initiates the electrical signals sent to the brain, producing the sensation of sweetness.