Extended Data Fig. 1: Single-particle cryo-EM analysis of human α1β3γ2L GABA_A receptor bound to the channel-blocker picrotoxin.

a, Representative micrograph of the PTX-bound GABA_A receptor particles embedded in vitreous ice. b, Representative 2D class averages. c, FSC curves for the 3D reconstruction using gold-standard refinement in RELION⁵⁶. Curves are shown for the phase randomization, unmasked, masked and phase-randomization-corrected masked maps. d, Validation of model refinement protocol. Curves are shown for model versus summed map (FSC_full), model refined in half-map 1 versus half-map 1 (FSC_work) and model refined in half-map 1 versus half-map 2 (FSC_free). e, The final, unsharpened cryo-EM map coloured by local resolution (estimated using MonoRes⁶¹) shown at a higher contour level (left) and at a lower level (middle and right) to highlight the nanodisc belt and flexible intracellular domains (ICDs). f, Angular distribution of particle projections. The map of the GABA_A receptor–PTX complex is shown in teal. g, Cryo-EM density segments for the PTX-binding site between residues 2ʹ and 9ʹ of the M2 transmembrane helices.