Supplementary Figure 5: The ion channel of the GlyRα3–glycine–AM-3607 complex in a desensitized state.
From: Crystal structures of human glycine receptor α3 bound to a novel class of analgesic potentiators
(a) Solvent contours of the transmembrane pore of the AM-3607 bound GlyRα3 pore showing the M2 helices of subunits A and C. Side chains of pore lining residues are shown. Numbering is according to the protein sequence and position in the M2 helix. Small purple, green and red spheres define a radius of >3.3 Å, 1.8-3.3 Å and <1.8 Å, respectively. (b), Contours of the glycine–ivermectin bound GlyRα1 pore, similar to panel (a). (c) Plot of pore radii as a function of distance along the pore axis for AM-3607 bound GlyRα3, glycine–ivermectin bound GlyRα1, ivermectin-bound GluClα, and benzamidine-bound GABAAR-β3. (d) Electrophysiological response to 30 μM glycine applied to HEK293T cells expressing human GlyRα3. Black (control) and blue (wash) traces are glycine application alone before and after co-application with 0.2 μM AM-3607 (red trace), showing potentiation of the glycine-induced current. (e) Desensitization of GlyRα3 upon stimulation with 1 mM glycine is not affected by subsequent co-application of 0.2 μM AM-3607.
