FIGURE 7.

Dual minima energy folding funnel for LacY as a function of membrane lipid composition. The folding of LacY to its lowest free energy state (ΔG) proceeds via a funnel-shaped energy landscape whose shape is defined by the physicochemical properties of the lipid environment (green, 75% PE; red, intermediate % PE; blue, 0% PE). The conformational space available to the population of folding proteins at a given lipid composition is defined by the funnel circumference (x axis) and the internal ΔG (y axis) of each folding intermediate. As LacY folds to lower energy conformations, it populates thermodynamic traps whose depth and shape determine the percent of the final native or inverted conformation at steady state. Membrane lipid composition affects a late folding event, which is postulated here to define a rapid equilibrium (horizontal arrow) between subsequent pathways leading to either the native or inverted conformation separated by a high thermodynamic barrier.