X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity.
The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. Genetic defects in ClC Cl- channels underlie several familial muscle and kidney diseases. Here we present the X-ray structures of two prokaryotic ClC Cl- channels from Salmonella enterica serovar typhimurium and Escherichia coli at 3.0 and 3.5 A, respectively. Both structures reveal two identical pores, each pore being formed by a separate subunit contained within a homodimeric membrane protein. Individual subunits are composed of two roughly repeated halves that span the membrane with opposite orientations. This antiparallel architecture defines a selectivity filter in which a Cl- ion is stabilized by electrostatic interactions with alpha-helix dipoles and by chemical coordination with nitrogen atoms and hydroxyl groups. These findings provide a structural basis for further understanding the function of ClC Cl- channels, and establish the physical and chemical basis of their anion selectivity.
Dutzler
Raimund
R
Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Campbell
Ernest B
EB
Cadene
Martine
M
Chait
Brian T
BT
MacKinnon
Roderick
R
D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry*; D018118:Chloride Channels / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry; D006801:Humans; D017136:Ion Transport; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D012486:Salmonella typhimurium; D017386:Sequence Homology, Amino Acid
D000838:Anions; D001426:Bacterial Proteins; D018118:Chloride Channels; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins