FIGURE 8.

Propofol docks at intersubunit sites in a GLIC closed state homology model. A, propofol docking to a GLIC closed state homology model built using the crystal structure of ELIC (PDB 2VL0) is shown. Propofol docked at two locations in the intersubunit interface; one site is under the M2-M3 loop between adjacent subunits (salmon and green), and the second site is a hydrophobic pocket bordered by the M3 and M1 helices of adjacent subunits near the cytoplasmic end of the TMD facing the lipid. Propofol docking poses are shown as yellow sticks overlaid with the Van der Waal's surface of the ensemble. B, an expanded top view of TMD of two adjacent subunits shows the docked propofol poses under the M2-M3 loop. C, an upright expanded view of two adjacent subunits shows the docked propofol poses near the cytoplasmic end of the TMD. D, propofol docking to GLIC crystal structure (PDB 3P50) is shown. Propofol docks in both the intra- and intersubunit cavities. In all panels, two adjacent subunits in the foreground are colored salmon and green, the mutated intersubunit residues Asn-238, Leu-240, and Glu-242 are orange sticks, and intrasubunit residues Ile-201, Val-241, and Thr-254 are blue sticks.