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Ion Binding and Selectivity of the Na+/H+ Antiporter MjNhaP1 from Experiment and Simulation.


ABSTRACT: Cells employ membrane-embedded antiporter proteins to control their pH, salt concentration, and volume. The large family of cation/proton antiporters is dominated by Na+/H+ antiporters that exchange sodium ions against protons, but homologous K+/H+ exchangers have recently been characterized. We show experimentally that the electroneutral antiporter NhaP1 of Methanocaldococcus jannaschii (MjNhaP1) is highly selective for Na+ ions. We then characterize the ion selectivity in both the inward-open and outward-open states of MjNhaP1 using classical molecular dynamics simulations, free energy calculations, and hybrid quantum/classical (QM/MM) simulations. We show that MjNhaP1 is highly selective for binding of Na+ over K+ in the inward-open state, yet it is only weakly selective in the outward-open state. These findings are consistent with the function of MjNhaP1 as a sodium-driven deacidifier of the cytosol that maintains a high cytosolic K+ concentration in environments of high salinity. By combining experiment and computation, we gain mechanistic insight into the Na+/H+ transport mechanism and help elucidate the molecular basis for ion selectivity in cation/proton exchangers.

SUBMITTER: Warnau J 

PROVIDER: S-EPMC6970264 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Ion Binding and Selectivity of the Na<sup>+</sup>/H<sup>+</sup> Antiporter MjNhaP1 from Experiment and Simulation.

Warnau Judith J   Wöhlert David D   Okazaki Kei-Ichi KI   Yildiz Özkan Ö   Gamiz-Hernandez Ana P AP   Kaila Ville R I VRI   Kühlbrandt Werner W   Hummer Gerhard G  

The journal of physical chemistry. B 20200102 2


Cells employ membrane-embedded antiporter proteins to control their pH, salt concentration, and volume. The large family of cation/proton antiporters is dominated by Na<sup>+</sup>/H<sup>+</sup> antiporters that exchange sodium ions against protons, but homologous K<sup>+</sup>/H<sup>+</sup> exchangers have recently been characterized. We show experimentally that the electroneutral antiporter NhaP1 of <i>Methanocaldococcus jannaschii</i> (MjNhaP1) is highly selective for Na<sup>+</sup> ions. We  ...[more]

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