Crystal structure of the cytoplasmic domain of the chloride channel ClC-0.
Ion channels are frequently organized in a modular fashion and consist of a membrane-embedded pore domain and a soluble regulatory domain. A similar organization is found for the ClC family of Cl- channels and transporters. Here, we describe the crystal structure of the cytoplasmic domain of ClC-0, the voltage-dependent Cl- channel from T. marmorata. The structure contains a folded core of two tightly interacting cystathionine beta-synthetase (CBS) subdomains. The two subdomains are connected by a 96 residue mobile linker that is disordered in the crystals. As revealed by analytical ultracentrifugation, the domains form dimers, thereby most likely extending the 2-fold symmetry of the transmembrane pore. The structure provides insight into the organization of the cytoplasmic domains within the ClC family and establishes a framework for guiding future investigations on regulatory mechanisms.
Department of Biochemistry, University of Zürich, Winterthurer Strasse 190, CH-8057 Zürich, Switzerland.
Sebastian
S
Meyer
Raimund
R
Dutzler
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018118:Chloride Channels / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000737:chemistry; D029941:Fish Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014101:Torpedo
D018118:Chloride Channels; D029941:Fish Proteins