Fig. 3: FLU/TET-induced RyR opening.
a Side view (top) and top view (bottom) of the pore forming domains of rRyR1 and chiRyRs. Structures compared include closed-state rRyR1 (PDB ID: 5TAQ), open-state rRyR1 (PDB ID: 5TAL), ref-chiRyR, chiRyR-FLU, chiRyR-TET, chiRyR-I4657M/G4819E, and chiRyR-I4657M/G4819E-CHL. The ion permeation pathway through the transmembrane pore is denoted by green dots (areas accessible to single H2O) and blue dots (areas accessible to double H2O). The diameters shown at bottom are the distances between two closest atoms from Ile4937 at diagonal positions of the channel gate. b Graph showing pore radii of different rRyR1 and chiRyRs structures, with the pore radius plotted against the channel coordinate. Selectivity filter (SF) and channel gate regions are highlighted by gray and purple shading, respectively. c Salt-bridge formed between Lys4563 and Asp4815 is broken upon the binding of FLU or TET. The densities of Lys4563 and Asp4815 in ref-chiRyR are shown at the 5σ level. The movement of Lys4563 is indicated by a red arrow, while the interaction between Lys4563 and Asp4815 is shown with a red dashed line. d, e Comparison of the diamide-binding sites in closed ref-chiRyR (ref-chiRyR-closed-HM: a homology model based on closed rRyR1 (PDB 5TAQ)), open ref-chiRyR, and chiRyR-FLU (d) chiRyR-TET (e). The binding of FLU/TET induces displacements in pVSD, S2-S3 and S4-S5 linkers compared to both closed and open ref-chiRyRs. The superposition was performed based on helices S1. The movements of transmembrane helices are illustrated by arrows. f Schematic cartoon showing that the binding of diamide insecticides induces the opening of the channel by pulling S2-S3 and S4-S5 linkers.
