Chemosensation underlies animal behavioral adaptation in ever-changing environments. As a member of the canonical transient receptor potential (TRP), TRPγ orchestrates the chemosensation and the adaptive behavior via fine motor control in Drosophila. Yet, how TRPγ senses and transduces chemical cues has been elusive. Here, we explore cryo-EM structures of dTRPγ in both native and camphor-bound states, with resolutions of 2.18 Å and 3.44 Å, respectively, thereby capturing ligand-induced pore dilation. Through analysis of dTRPγ channel structure, we further identify two allosteric Ca2+-sensing modules: an activating site embedded within the voltage-sensor-like domain (VSLD) and an inhibitory site coordi... More
Chemosensation underlies animal behavioral adaptation in ever-changing environments. As a member of the canonical transient receptor potential (TRP), TRPγ orchestrates the chemosensation and the adaptive behavior via fine motor control in Drosophila. Yet, how TRPγ senses and transduces chemical cues has been elusive. Here, we explore cryo-EM structures of dTRPγ in both native and camphor-bound states, with resolutions of 2.18 Å and 3.44 Å, respectively, thereby capturing ligand-induced pore dilation. Through analysis of dTRPγ channel structure, we further identify two allosteric Ca2+-sensing modules: an activating site embedded within the voltage-sensor-like domain (VSLD) and an inhibitory site coordinated by the intracellular ankyrin repeat domain (ARD) and coiled-coil domain (CCD). These spatially segregated sensors convert cytoplasmic Ca2+ into opposing gating signals, maintaining calcium homeostasis via a dual-feedback manner. In vivo, this bidirectional regulation directly controls locomotor kinematics by modulating stride length and velocity, while mutants with lost Ca2+regulatory functions exhibit impaired locomotor activity. Together, our findings reveal that dTRPγ acts as an independent ion channel, integrating environmental cues with ionic dynamics to drive adaptive behavior.
