Mechanism of Na+/H+ antiporting

Isaiah T. Arkin, Huafeng Xu, Morten Jensen, Eyal Arbely, Estelle R. Bennett, Kevin J. Bowers, Edmond Chow, Ron O. Dror, Michael P. Eastwood, Ravenna Flitman-Tene, Brent A. Gregersen, John L. Klepeis, István Kolossváry, Yibing Shan, David E. Shaw*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

129 Scopus citations


Na+/H+ antiporters are central to cellular salt and pH homeostasis. The structure of Escherichia coli NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function. Three conserved aspartates are key to our proposed mechanism: Asp164 (D164) is the Na+-binding site, D163 controls the alternating accessibility of this binding site to the cytoplasm or periplasm, and D133 is crucial for pH regulation. Consistent with experimental stoichiometry, two protons are required to transport a single Na+ ion: D163 protonates to reveal the Na+-binding site to the periplasm, and subsequent protonation of D164 releases Na+. Additional mutagenesis experiments further validated the model.

Original languageAmerican English
Pages (from-to)799-803
Number of pages5
Issue number5839
StatePublished - 10 Aug 2007


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