Fig. 2: The conserved hydrophobic pocket preferentially binds to phospholipid.
From: Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red
a A cross-section of human CALHM1 shows the location of the hydrophobic pocket filled with a phospholipid. Residues that form the hydrophobic pocket are shown in stick representation. There are eight hydrophobic pockets per CALHM1 octamer. The inset shows a zoomed-in view of the hydrophobic pocket viewed from the pore. Residues are numbered in red (TMD3 and TMD4) or green (TMD2). b Coarse-grained PMF calculations suggest that binding of POPC into this pocket is thermodynamically favored over that of cholesterol with energy minimums of approximately −6.4 kcal/mol and −1.9 kcal/mol, respectively (right). The arrow indicates the direction of steering for which the reaction coordinate was generated (left). The steered POPC molecule is colored from yellow to red according to progress along the steered MD simulation, with light yellow beads representing POPC at the start, and red beads at the end of the steered MD. Two other bound POPC molecules are shown in blue, brown and green beads, representing different bead types. Error bands are 1 standard deviation generated from 200 rounds of bootstrap analysis.
