CLC channels and transporters: proteins with borderline personalities

Biochim Biophys Acta. 2010 Aug;1798(8):1457-64. doi: 10.1016/j.bbamem.2010.02.022. Epub 2010 Feb 24.


Controlled chloride movement across membranes is essential for a variety of physiological processes ranging from salt homeostasis in the kidneys to acidification of cellular compartments. The CLC family is formed by two, not so distinct, sub-classes of membrane transport proteins: Cl(-) channels and H(+)/Cl(-) exchangers. All CLC's are homodimers with each monomer forming an individual Cl- permeation pathway which appears to be largely unaltered in the two CLC sub-classes. Key residues for ion binding and selectivity are also highly conserved. Most CLC's have large cytosolic carboxy-terminal domains containing two cystathionine beta-synthetase (CBS) domains. The C-termini are critical regulators of protein trafficking and directly modulate Cl- by binding intracellular ATP, H+ or oxidizing compounds. This review focuses on the recent mechanistic insights on the how the structural similarities between CLC channels and transporters translate in unexpected mechanistic analogies between these two sub-classes.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiporters / chemistry
  • Antiporters / metabolism
  • Binding Sites
  • Chloride Channels / chemistry
  • Chloride Channels / metabolism*
  • Chlorides / metabolism
  • Humans
  • Ion Transport
  • Models, Anatomic
  • Nucleotides / metabolism
  • Protein Structure, Tertiary
  • Protons


  • Antiporters
  • Chloride Channels
  • Chlorides
  • Nucleotides
  • Protons
  • hydrogen-chloride symporter