Fig. 1: Structure of the AMPAR allosterically inhibited state.
From: Allosteric competition and inhibition in AMPA receptors
a, Schematic representation of the AMPAR gating cycle. Only two of four subunits are shown for illustration purposes. b, Concentration-dependent inhibition by GYKI-52466 of GluA2-γ2EM residual currents in the presence of 1 mM Glu and 100 μM CTZ using nonlinear curve fit approach with the Levenberg–Marquardt iteration algorithm. For each concentration, data were obtained from at least three different cells. IC50 = 43.20 ± 6.61 μM; P = 0.00022. c, Ribbon illustration detailing the structure of the AMPAR inhibited state, GluA2-γ2IS-1. GluA2 subunits are purple (A and C) or orange (B and D) depending on their positions. GYKI-52466 (pink) is bound at all four TMD collar regions and each LBD clamshell is closed around Glu (green). TARPγ2 subunits (light blue) occupy all four auxiliary sites around the receptor. d, High-resolution details of the focused GluA2 TMD from cryo-EM reconstruction. Left: side view of the GluA2 TMD showing the M3 bundle crossing in a closed conformation. Right: top view showing the bundle crossing constricting access to the ion channel (red, dashed) and the relative location of the channel collar (yellow, dashed) with GYKI-52466 bound to all four GluA2 subunits. Lipids (blue) adorn the AMPAR TMD. e, Plot of the ion channel radius along the pore axis showing a constriction at the M3 bundle crossing gate. The dashed line represents the radius of a water molecule.
