Transport cycle of LacY. (a) Overview of the postulated steps in the transport model. Inward-facing (green) and outward-facing (blue) conformations are separated by the apo-intermediate conformations (orange) or by the occluded-intermediate conformations (gray). Steps are numbered consecutively: 1: opening of the site; 2: deprotonation to inside and reorientation to the apo intermediate with a central cavity closed to either side of the membrane; 3: opening of the outward-facing cavity and reprotonation from the outside; 4: formation of outward-open, substrate-free conformation; 5 and 6: substrate binding and induced fit to the occluded conformation; 7: opening of the inward-facing cavity and release of the sugar; and 8: formation of the protonated, substrate-free conformation. The blue-shaded area demarcates the equilibrium-exchange reaction. (b) Hypothetical energy profile for the transport cycle. Conformations shown in (a) are translated into relative energy states (indicated by the icons of conformations defined in (a) with the cytoplasmic side of the symporter facing up). The schemes are cycles read by following the arrowheads. The red part of the cycle represents the transitions between Steps 1 and 4 of the empty pathway. The blue line corresponds to Steps for net sugar transporting steps and for the exchange reaction. The hypothetical effect of an imposed is shown as a broken black vertical arrow, and the broken red lines show the resulting energy profile. The figure is modified from [39].