Substrate-dependent reversal of anion transport site orientation in the human red blood cell anion-exchange protein, AE1.

The tightly coupled, one-for-one exchange of anions mediated by the human red blood cell AE1 anion-exchange protein involves a ping-pong mechanism, in which AE1 alternates between a state with the anion-binding site facing inward toward the cytoplasm (Ei) and a state with the site facing outward toward the external medium (Eo). The conformational shift (Ei <--> Eo) is only permitted when a suitable substrate such as Cl(-) or HCO(3)(-) (B(-)) is bound. With no anions bound, or with Cl(-) bound, far more AE1 molecules are in the inward-facing than the outward-facing forms (Ei Eo, ECli EClo).