CLC-0 and CFTR: chloride channels evolved from transporters.
CLC-0 and cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels play important roles in Cl(-) transport across cell membranes. These two proteins belong to, respectively, the CLC and ABC transport protein families whose members encompass both ion channels and transporters. Defective function of members in these two protein families causes various hereditary human diseases. Ion channels and transporters were traditionally viewed as distinct entities in membrane transport physiology, but recent discoveries have blurred the line between these two classes of membrane transport proteins. CLC-0 and CFTR can be considered operationally as ligand-gated channels, though binding of the activating ligands appears to be coupled to an irreversible gating cycle driven by an input of free energy. High-resolution crystallographic structures of bacterial CLC proteins and ABC transporters have led us to a better understanding of the gating properties for CLC and CFTR Cl(-) channels. Furthermore, the joined force between structural and functional studies of these two protein families has offered a unique opportunity to peek into the evolutionary link between ion channels and transporters. A promising byproduct of this exercise is a deeper mechanistic insight into how different transport proteins work at a fundamental level.
Chen
Tsung-Yu
TY
Center for Neuroscience and Department of Neurology, University of California, Davis, California 95618, USA. tycchen@ucdavis.edu
Hwang
Tzyh-Chang
TC
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D019143:Evolution, Molecular; D049810:Genetic Speciation; D006801:Humans; D005810:Multigene Family; D011487:Protein Conformation
D018528:ATP-Binding Cassette Transporters; C505032:CFTR protein, human; C120501:CLC-0 chloride channel protein, Torpedo californica; D018118:Chloride Channels; C508370:ClC protein, E coli; D029968:Escherichia coli Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator