Structural basis for sugar perception by Drosophila gustatory receptors.

Insects rely on a family of seven-transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities such as sweet and bitter. Here we report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels, composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBD, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBD. Sugar binding to LBD induces local conformational changes, which are subsequently transferred to PD to cause channel opening. Our studies have revealed structural basis for sugar recognition and activation of GRs.