Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels

Nature. 2004 Feb 26;427(6977):803-7. doi: 10.1038/nature02314.


ClC Cl- channels make up a large molecular family, ubiquitous with respect to both organisms and cell types. In eukaryotes, these channels fulfill numerous biological roles requiring gated anion conductance, from regulating skeletal muscle excitability to facilitating endosomal acidification by (H+)ATPases. In prokaryotes, ClC functions are unknown except in Escherichia coli, where the ClC-ec1 protein promotes H+ extrusion activated in the extreme acid-resistance response common to enteric bacteria. Recently, the high-resolution structure of ClC-ec1 was solved by X-ray crystallography. This primal prokaryotic ClC structure has productively guided understanding of gating and anion permeation in the extensively studied eukaryotic ClC channels. We now show that this bacterial homologue is not an ion channel, but rather a H+-Cl- exchange transporter. As the same molecular architecture can support two fundamentally different transport mechanisms, it seems that the structural boundary separating channels and transporters is not as clear cut as generally thought.

MeSH terms

  • Animals
  • Antiporters / chemistry
  • Antiporters / genetics
  • Antiporters / metabolism*
  • Biological Transport, Active
  • Chloride Channels / chemistry
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Chlorides / metabolism
  • Electric Conductivity
  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Ion Transport
  • Models, Biological
  • Models, Molecular
  • Mutation, Missense / genetics
  • Prokaryotic Cells / chemistry
  • Prokaryotic Cells / metabolism
  • Protein Conformation
  • Protons
  • Structure-Activity Relationship


  • Antiporters
  • Chloride Channels
  • Chlorides
  • Escherichia coli Proteins
  • Protons