The past and present of sodium energetics: may the sodium-motive force be with you

Abstract

All living cells routinely expel Na(+) ions, maintaining lower concentration of Na(+) in the cytoplasm than in the surrounding milieu. In the vast majority of bacteria, as well as in mitochondria and chloroplasts, export of Na(+) occurs at the expense of the proton-motive force. Some bacteria, however, possess primary generators of the transmembrane electrochemical gradient of Na(+) (sodium-motive force). These primary Na(+) pumps have been traditionally seen as adaptations to high external pH or to high temperature. Subsequent studies revealed, however, the mechanisms for primary sodium pumping in a variety of non-extremophiles, such as marine bacteria and certain bacterial pathogens. Further, many alkaliphiles and hyperthermophiles were shown to rely on H(+), not Na(+), as the coupling ion. We review here the recent progress in understanding the role of sodium-motive force, including (i) the conclusion on evolutionary primacy of the sodium-motive force as energy intermediate, (ii) the mechanisms, evolutionary advantages and limitations of switching from Na(+) to H(+) as the coupling ion, and (iii) the possible reasons why certain pathogenic bacteria still rely on the sodium-motive force.

Figure 1. Similar and distinct features in the organization of prokaryotic F- and V-type ATPases

Homologous subunits in the two types of ATPases are indicated by identical colors and shapes, whereas analogous by evolutionarily unrelated subunits of the central stalk are shown by different colors and shapes. Subunits that show structural analogy but do not appear to be homologous are shown by different but similar colors. The dual notation of some V-ATPase subunits (e.g., c/K) reflects their designations in eukaryotic and prokaryotic V-ATPases, respectively. For further details, see ref. [53].

Figure 2. Similar structural organization of membrane rotor subunits and their Na⁺-binding sites in the F- and V-type Na⁺-translocating ATP synthases

The structures were drawn by using the VMD software package [123]. Left panel, a single K subunit of the Na⁺-translocating V-type ATP synthase of Enterococcus chirae (Protein Data Bank entry 2BL2 [65]); right panel, two c subunits, A (cyan) and B (ice-blue), of the Na⁺-translocating F-type ATP synthase of Ilyobacter tartaricus (Protein Data Bank entry 1YCE [64]). In both structures, the Na⁺ ion is shown as a purple ball, amino acid residues that coordinate the Na⁺ ion are shown in stick representation and colored. The principal Na⁺-coordinating Glu residue (Glu65A in I. tartaricus and Glu139 in E. hirae) is colored red; other Na⁺ ligands are colored as follows: Gln32A in I. tartaricus and Gln110 in E. hirae, blue; Ser66B in I. tartaricus and Thr64 in E. hirae, tan; Val63B in I. tartaricus and Leu61 in E. hirae (which coordinate Na+ with their backbone carbonyls), green. One more bond is provided by a grey-colored Gln65 in E. hirae and, via a water molecule, by a Thr67B in I. tartaricus (T. Meier, personal communication). The remaining sixth bond is provided, most likely, by the unseen water molecules as discussed in more detail elsewhere [30]. The Tyr residue (Tyr70B in I. tartaricus and Tyr68 in E. hirae) that is important for stabilization of the principal Na⁺-binding Glu residue [58] is colored yellow.