CLC channels and transporters: proteins with borderline personalities.
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.
Accardi
Alessio
A
Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. ala2022@med.cornell.edu
Picollo
Alessandra
A
D000818:Animals; D017920:Antiporters / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D018118:Chloride Channels / Q000737:chemistry / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008953:Models, Anatomic; D009711:Nucleotides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011522:Protons
D017920:Antiporters; D018118:Chloride Channels; D002712:Chlorides; D009711:Nucleotides; D011522:Protons; C114260:hydrogen-chloride symporter