NhaA of Escherichia coli, as a model of a pH-regulated Na+/H+antiporter

Biochim Biophys Acta. 2004 Jul 23;1658(1-2):2-13. doi: 10.1016/j.bbabio.2004.04.018.


Na(+)/H(+) antiporters are ubiquitous membrane proteins that are involved in homeostasis of H(+) and Na(+) throughout the biological kingdom. Corroborating their role in pH homeostasis, many of the Na(+)/H(+) antiporter proteins are regulated directly by pH. The pH regulation of NhaA, the Escherichia coli Na(+)/H(+) antiporter (EcNhaA), as of other, both eukaryotic and prokaryotic Na(+)/H(+) antiporters, involves a pH sensor and conformational changes in different parts of the protein that transduce the pH signal into a change in activity. Thus, residues that affect the pH response, the translocation or both activities cluster in separate domains along the antiporter molecules. Importantly, in the NhaA family, these domains are conserved. Helix-packing model of EcNhaA based on cross-linking data suggests, that in the three dimensional structure of NhaA, residues that affect the pH response may be in close proximity, forming a single pH sensitive domain. Therefore, it is suggested that, despite considerable differences in the primary structure of the antiporters from the bacterial NhaA to the mammalian NHEs, their three-dimensional architectures are conserved. Test of this possibility awaits the atomic resolution of the 3D structure of the antiporters.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Escherichia coli
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Eukaryotic Cells / metabolism
  • Homeostasis
  • Hydrogen-Ion Concentration
  • Molecular Sequence Data
  • Mutation
  • Prokaryotic Cells / metabolism
  • Protein Conformation
  • Signal Transduction
  • Sodium-Hydrogen Exchangers / chemistry*
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / metabolism*
  • Vibrio cholerae


  • Escherichia coli Proteins
  • NhaA protein, E coli
  • Sodium-Hydrogen Exchangers