An internal latch lets one pufferfish taste receptor accept amino acids of either handedness

The latch is a set of contacts between subdomains inside the receptor's extracellular binding region. In a class C G protein-coupled receptor, that region is shaped like a clamshell: a matching nutrient drops into the cleft and the clamp closes, and the closed state is what starts intracellular signaling, while a ligand of the wrong shape or the mirror-image chirality leaves the clamp open and the cascade quiet ^[6]. In the pufferfish receptor, bridges across the subdomains brace the cleft shut even when the fit is imperfect, holding the active conformation across a wide range of amino acids ^[7]. The team identified them from the crystal structure together with mutational analysis ^[7].

"Normally, a receptor is unable to bind to a molecule that is the wrong shape," senior author Atsuko Yamashita said ^[9].

In mammals the L-selective umami receptor is TAS1R1/TAS1R3, and the receptor that reads sugars and D-amino acids is TAS1R2/TAS1R3 ^[3]. The two pairings share the TAS1R3 subunit, and between them they split ligand classes that the single pufferfish Tas1r1/Tas1r3 pairing covers on its own ^[13]. The Osaka group describes that as a receptor expanding its range by acquiring intramolecular interactions that shift the conformational equilibrium toward the active state, with no new gene family required ^[8].

The crystal structure covers the ligand-binding domain, not the transmembrane part of the receptor that couples to a G protein ^[1]. How much signaling the latch mutants lost relative to wild type is in the paper; neither published summary reports it ^[14].

The evolutionary account is offered as an inference, and the authors say so. "We believe that the pufferfish's diet drives this molecular evolution," Yamashita said. "They eat a lot of mollusks and crustaceans, which contain high amounts of D-amino acids" ^[10]. The structure does not date the adaptation, and the sources report no comparison against fish with different diets ^[15].

The team expects the work to inform new umami flavors for humans and feed for livestock and fisheries ^[11]. The fisheries end is the nearer of the two: a fish receptor, fish ligands, and an outcome you can measure as feed intake. Designing a compound for human tongues runs through the human umami receptor, whose ligand recognition has stayed structurally obscure because purifying and stabilizing these fragile complexes in vitro has proved difficult ^[12].