Structural basis for sugar perception by Drosophila gustatory receptors

Abstract

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.

Structural basis of odor sensing by insect heteromeric odorant receptors

“…1D). The overall tetrameric assembly of the Aa OR10-Orco heteromer closely resembles that of previously described homotetrameric members of this family, such as the Mh OR5 from the jumping bristletail Machilis hrabei ( 11 ) and related insect gustatory receptors ( 32 – 34 ). Most of the protein is embedded within the membrane plane, and a small “anchor” domain protrudes into the intracellular space (Fig.…”

“…At the base of this vestibule, ions flow through four lateral conduits into the intracellular space in a quadrivial pore architecture (Fig. 2C), analogous to what has been observed in structures of homotetrameric members of this family ( 11 , 14 , 32 – 34 ).…”

The novel function of an orphan pheromone receptor reveals the sensory specializations of two potential distinct types of sex pheromones in noctuid moth

“…This observation is reminiscent of the substrate binding induced conformational shifts observed in the recently resolved cryo-EM homotetrameric structures of gustatory receptors (Gr), such as Drosophila melanogaster Gr43a (DmGr43a) and B. mori Gr9 (BmGr9) in both close and open states [62][63][64], which facilitate ion passage by rotating helices and repositioning the side chains of hydrophobic (F422 in Gr43a, F444 in BmGr9) and hydrophilic residues (Q421 in Gr43a, Q443 in BmGr9) at the entrance of the channel (Fig. 7C).…”

Exploration-exploitation trade-off is regulated by metabolic state and taste value inDrosophila

“…These findings indicate a redundancy within the fly gustatory system for sucrose detection and align with the hypothesis that diverse sugar receptor genes form a heteromeric receptor complex for detecting various sugar molecules. 72–74 Furthermore, our data suggests that sensory detection of sucrose rather than post-ingestive nutrient signals appears to drive the switch in feeding and foraging behaviors. Our results are consistent with the previous reports demonstrating that the activation of sugar-sensing taste neurons, even without a food source, is sufficient to alter the foraging strategy of flies.…”