Figure 1. Structure of the AMPAR inhibited state.

a) Schematic representation of the AMPAR gating cycle. b) Ribbon illustration detailing the structure of the AMPAR inhibited state, IS-1. GluA2 subunits are purple (A/C) or orange (B/D) depending on their positions. GYKI-52466 (pink) is bound at all four TMD collar regions and each LBD clamshell is closed around glutamate (green). TARPγ2 subunits (light blue) occupy all four auxiliary sites around the receptor. c) High resolution details of the focused GluA2 TMD from cryo-EM reconstruction. Side view (top) of the GluA2 TMD from showing the M3 bundle crossing in a closed conformation and top view (bottom) showing the bundle crossing constricting access to the ion channel (green, 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. d) Plot of the ion channel radius along the pore axis showing a constriction at the M3 bundle crossing gate. Dashed line represents the radius of a water molecule.