title: CLC chloride channels: correlating structure with function.
abstract: CLC chloride channels form a large gene family that is found in bacteria, archae and eukaryotes. Previous mutagenesis studies on CLC chloride channels, combined with electrophysiology, strongly supported the theory that these channels form a homodimeric structure with one pore per subunit (a'double-barrelled' channel), and also provided clues about gating and permeation. Recently, the crystal structures of two bacterial CLC proteins have been obtained by X-ray diffraction analysis. They confirm the double-barrelled architecture, and reveal a surprisingly complex and unprecedented channel structure. At its binding site in the pore, chloride interacts with the ends of four helices that come from both sides of the membrane. A glutamate residue that protrudes into the pore is proposed to participate in gating. The structure confirms several previous conclusions from mutagenesis studies and provides an excellent framework for their interpretation.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, Falkenried 94, Germany.
authors.forename: Raúl
authors.initials: R
authors.lastname: Estévez
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Jentsch
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics; D018118:Chloride Channels / Q000737:chemistry* / Q000145:classification / Q000235:genetics*; D003460:Crystallization; D018360:Crystallography, X-Ray; D003541:Cystathionine beta-Synthase / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry; D015640:Ion Channel Gating / Q000502:physiology*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D018118:Chloride Channels; D046911:Macromolecular Substances; D008565:Membrane Proteins; D018698:Glutamic Acid; D003541:Cystathionine beta-Synthase