FIGURE 4: Mutations in ELIC-α1GABA_AR ablate neurosteroid thermal stabilization.

(A) Structure of the α1GABA_AR-TMD highlighting the residues photolabeled by 100 μM KK123 (blue) or KK200 (red) in WT, and showing a representative docking pose for allopregnanolone (yellow) at both intersubunit and intrasubunit sites. Two adjacent subunits are shown and the channel pore is behind these subunits. A zoomed-in box of the intersubunit site shows the chains of residues where mutations were made (Q242-green, W246-orange). (B) The percent intensity of ELIC-α1GABA_AR WT or mutant pentamer peaks relative to 4 °C after heating to a temperature that causes 70% peak decay (65 °C for WT; 52 °C for Q242L; 68 °C for Q242W; 60 °C for W246L). 10 μM allopregnanolone (3α5αP) thermally stabilizes WT but not the mutants (n = 3, ± SEM). **P < 0.01 vs. control.