Fig. 3: DID and ZOL binding propagates conformational changes to the TMD.
From: Cryo-EM structures reveal native GABAA receptor assemblies and pharmacology
a, Competitive radioligand binding assay for purified nα1-GABAARs in complex with ZOL or DID. Individual data points are plotted, along with the curve fitted with the one-site model. b, Structural overview of the two-Fab receptor α1*-β2-α1-β2*-γ2 nα1-GABAAR (*denotes the subunit is next to the γ2 subunit) in complex with ZOL, GABA and endogenous neurosteroid (NS). c,d, Binding poses of DID (c) and ZOL (d) and cryo-EM ligand density. Blue dashed lines, π–π/CH interactions; black dashed lines, hydrogen bonds less than 3.5 Å (acceptor to donor); grey dashed lines, weak hydrogen bonds between 3.5 Å and 4 Å. Cryo-EM density around DID and ZOL is contoured at 5.7σ and 5.1σ, respectively. e, Effect of ligand binding on ECD arrangement. Coordinates of the closed resting receptor in complex with picrotoxin (PTX) are from PDB 6HUG. Structures superimposed on the basis of global TMD. Individual ECDs displaced from centre of pore by 15 Å for clarity. f, Pore profiles in DID structure and ZOL/GABA structure. Pore-delineating dots coloured according to pore radius at that position: red, less than 1.8 Å; green, between 1.8 Å and 4 Å; blue, more than 4 Å.
