title: Structural basis for ion conduction and gating in ClC chloride channels.
abstract: Members of the ClC family of voltage-gated chloride channels are found from bacteria to mammals with a considerable degree of conservation in the membrane-inserted, pore-forming region. The crystal structures of the ClC channels of Escherichia coli and Salmonella typhimurium provide a structural framework for the entire family. The ClC channels are homodimeric proteins with an overall rhombus-like shape. Each ClC dimer has two pores each contained within a single subunit. The ClC subunit consists of two roughly repeated halves that span the membrane with opposite orientations. This antiparallel architecture defines a chloride selectivity filter within the 15-A neck of a hourglass-shaped pore. Three Cl(-) binding sites within the selectivity filter stabilize ions by interactions with alpha-helix dipoles and by chemical interactions with nitrogen atoms and hydroxyl groups of residues in the protein. The Cl(-) binding site nearest the extracellular solution can be occupied either by a Cl(-) ion or by a glutamate carboxyl group. Mutations of this glutamate residue in Torpedo ray ClC channels alter gating in electrophysiological assays. These findings reveal a form of gating in which the glutamate carboxyl group closes the pore by mimicking a Cl(-) ion.
authors.affiliation: Department of Biochemistry, University of Zurich, Winterthurerstr. 190, CH-8057 Zurich, Switzerland. dutzler@bioc.unizh.ch
authors.forename: Raimund
authors.initials: R
authors.lastname: Dutzler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018118:Chloride Channels / Q000737:chemistry* / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D015221:Potassium Channels