2.A.49.2.11
The voltage-gated torpedo chloride channel, CLC-0, of 810 aas. This channel is thought to ensure the high conductance of the non-innervated membrane of the electrocyte necessary for efficient current generation caused by sodium influx through the acetylcholine receptor at the innervated membrane.  ClC-0 is a homodimer with separate pores in each subunit. Each protopore can be opened and closed independently from the other pore by a ""fast gate"". A common, slow gate acts on both pores simultaneously. The opening of the fast gate is controlled by a critical glutamate (E166), whose protonation state determines the fast gate's pH dependence (Zifarelli and Pusch 2010). Extracellular protons likely arrive directly at E166, but protonation of E166 from the inside may be mediated by the dissociation of an intrapore water molecule. The OH^- anion resulting from dissociation of water is stabilized in one of the anion binding sites of the channel, competing with intracellular Cl^-. Proton translocation drives irreversible gating transitions associated with the slow gate (Zifarelli and Pusch 2010). The structure of the cytoplasmic domain has been solved (Meyer and Dutzler 2006). It contains a folded core of two tightly interacting cystathionine beta-synthetase (CBS) subdomains which are connected by a 96 residue mobile linker. The domains form dimers, thereby extending the 2-fold symmetry of the transmembrane pore.