Common Internal Allosteric Network Links Anesthetic Binding Sites in a Pentameric Ligand-Gated Ion Channel
Red denotes lowest occupancy and blue denotes highest occupancy. Propofol occupancy is shown in (a) and generic nonpolar particle occupancy is shown in (b). For comparison, propofol (PDB 3P50) and ketamine (PDB 4F8H) are shown in their crystallographic positions determined by structural alignment of protein backbones, in yellow and green respectively. Ile202, Val242, Thr255, important in propofol binding, are indicated. Histograms of occupancy by residue index are shown in (c), (d), with domains shaded as follows: TM1: yellow, TM2: green, TM3: orange, TM4: red. Occupancy units (y-axis) are proportions with maximum 1. Occupancies are combined across subunits. Note broadly similar profiles from residue index 200 and greater, indicating an occupancy pattern in the transmembrane domain shared between propofol and the generic nonpolar particle.