Specific protonation of acidic residues confers K⁺ selectivity to the gastric proton pump.

ABSTRACT: The gastric proton pump (H⁺,K⁺-ATPase) transports a proton into the stomach lumen for every K⁺ ion exchanged in the opposite direction. In the lumen-facing state of the pump (E2), the pump selectively binds K⁺ despite the presence of a 10-fold higher concentration of Na⁺. The molecular basis for the ion selectivity of the pump is unknown. Using molecular dynamics simulations, free energy calculations, and Na⁺ and K⁺-dependent ATPase activity assays, we demonstrate that the K⁺ selectivity of the pump depends upon the simultaneous protonation of the acidic residues E343 and E795 in the ion-binding site. We also show that when E936 is protonated, the pump becomes Na⁺ sensitive. The protonation-m

SUBMITTER: Madapally HV 

PROVIDER: S-EPMC10825007 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature