Na+/H+ antiporters

Etana Padan*, Miro Venturi, Yoram Gerchman, Nir Dover

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

311 Scopus citations

Abstract

Na+/H+ antiporters are membrane proteins that play a major role in pH and Na+ homeostasis of cells throughout the biological kingdom, from bacteria to humans and higher plants. The emerging genomic sequence projects already have started to reveal that the Na+/H+ antiporters cluster in several families. Structure and function studies of a purified antiporter protein have as yet been conducted mainly with NhaA, the key Na+/H+ antiporter of Escherichia coli. This antiporter has been overexpressed, purified and reconstituted in a functional form in proteoliposomes. It has recently been crystallized in both 3D as well as 2D crystals. The NhaA 2D crystals were analyzed by cryoelectron microscopy and a density map at 4 Å resolution was obtained and a 3D map was reconstructed. NhaA is shown to exist in the 2D crystals as a dimer of monomers each composed of 12 transmembrane segments with an asymmetric helix packing. This is the first insight into the structure of a polytopic membrane protein. Many Na+/H+ antiporters are characterized by very dramatic sensitivity to pH, a property that corroborates their role in pH homeostasis. The molecular mechanism underlying this pH sensitivity has been studied in NhaA. Amino acid residues involved in the pH response have been identified. Conformational changes transducing the pH change into a change in activity were found in loop VIII-IX and at the N-terminus by probing trypsin digestion or binding of a specific monoclonal antibody respectively. Regulation by pH of the eukaryotic Na+/H+ antiporters involves an intricate signal transduction pathway (recently reviewed by Yun et al., Am. J. Physiol. 269 (1995) G1-G11). The transcription of NhaA has been shown to be regulated by a novel Na+-specific regulatory network. It is envisaged that interdisciplinary approaches combining structure, molecular and cell biology as well as genomics should be applied in the future to the study of this important group of transporters.

Original languageEnglish
Pages (from-to)144-157
Number of pages14
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1505
Issue number1
DOIs
StatePublished - 1 May 2001

Keywords

  • Active transport
  • Homeostasis of Na and H
  • Membrane protein
  • Sodium ion/proton antiporter

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