Extended Data Fig. 7: Disease mutations associated with α1, β3 and γ2, lateral tunnels and fenestrations at the subunit interfaces.

a, b, Disease mutations associated with GABA_A α1, β3 and γ2 subunits are mapped onto the structure and shown in sphere representation. The receptor is viewed parallel to the membrane plane (a) and from the extracellular aspect (b). Outlined boxes highlight the position of mutations shown in c–e. c–e, Close-up view of disease mutations associated with the α1 and β3 subunits. Polar interactions between residues are shown as dotted lines. f, Table summarizing several disease mutations identified in genes for α1, β3 and γ2. Functional effects as determined from experimental studies^{52,53,54,55,56,57,58} of channel properties are summarized. g, Exposed surface of the γ2/β3 subunit interface coloured according to electrostatic surface potential. h, Close-up view of an electronegative fenestration formed at the γ2/β3 extracellular domain interface. The continuous tunnel leading from extracellular space to the receptor vestibule is outlined. i, Exposed surface of the α1/β3 subunit interface coloured according to electrostatic surface potential. j, Close-up view of the α1/β3 extracellular interface reveals an upper tunnel leading to the mid-portion of the ECD vestibule. A lower tunnel (denoted by the arrow) opens into the upper aspect of the ion channel at the level of β3His267, a residue that is implicated in mediating the effects of propofol⁵⁹.