Crystal structure of the Na/H antiporter NhaA at active pH reveals the mechanistic basis for pH sensing.

The strict exchange of protons for sodium ions across cell membranes by NaH exchangers is a fundamental mechanism for cell homeostasis. At active pH, Na/H exchange can be modelled as competition between H and Na to an ion-binding site, harbouring either one or two aspartic-acid residues. Nevertheless, extensive analysis on the model Na/H antiporter NhaA from Escherichia coli, has shown that residues on the cytoplasmic surface, termed the pH sensor, shifts the pH at which NhaA becomes active.

Dissecting the proton transport pathway in electrogenic Na/H antiporters.

Sodium/proton exchangers of the family mediate the transport of protons in exchange for sodium to help regulate intracellular pH, sodium levels, and cell volume. In electrogenic Na/H antiporters, it has been assumed that two ion-binding aspartate residues transport the two protons that are later exchanged for one sodium ion. However, here we show that we can switch the antiport activity of the bacterial Na/H antiporter NapA from being electrogenic to electroneutral by the mutation of a single lysine residue (K305).

Crystal structures reveal the molecular basis of ion translocation in sodium/proton antiporters.

To fully understand the transport mechanism of Na(+)/H(+) exchangers, it is necessary to clearly establish the global rearrangements required to facilitate ion translocation. Currently, two different transport models have been proposed. Some reports have suggested that structural isomerization is achieved through large elevator-like rearrangements similar to those seen in the structurally unrelated sodium-coupled glutamate-transporter homolog GltPh.