Fig. 7. Hypothetical elevator-like movement of the core domains facilitated or inhibited by anion binding.

Prestin dimers with the core domain (“Core”, purple) and the gate domain (“Gate”, blue) are shown with the plasma membrane (gray lines), with the extracellular (Exo) and cytosolic (Cyto) sides indicated. Gray arrows indicate the electric field. a Unbound state. The highly positively charged central pocket (indicated by “+”) is forcibly exposed toward the intracellular solvent in the absence of an anion. b Anion binding allows the core domain to adopt the occluded state. Pink arrows indicate the elevator-like motion of the core domain movement with respect to the gate domain. Anion binding neutralizes the positive charge at the anion-binding pocket macroscopically. However, microscopic charge biases likely remain, which may serve as the voltage sensor of prestin. c Salicylate binding to the positively charged central pocket, but sterically inhibits the transition from the inward-open to the occluded state.