FIGURE 11-26 Operational model for the two-Na⁺/one-glucose symporter. Simultaneous binding of Na⁺ and glucose to the conformation with outward-facing binding sites (step 1) causes a conformational change in the protein such that the bound substrates are transiently occluded, unable to dissociate into either medium (step 2). In step 3, the protein assumes a third conformation with inward-facing sites. Dissociation of the bound Na⁺ and glucose (step 4) allows the protein to revert to its original outward-facing conformation (step 5), ready to transport additional substrate. See H. Krishnamurthy et al., 2009, Nature 459:347–355 for details on the structure and function of this and related Na⁺-linked symporters.