Homodimeric architecture of a ClC-type chloride ion channel.

The recent discovery of the ClC-family of anion-conducting channel proteins has led to an appreciation of the central roles played by chloride ion channels in cellular functions, such as electrical behaviour of muscle and nerve and epithelial solute transport. Little is known, however, about molecular architecture or sequence-function relationships in these membrane proteins. In the single case of ClC-0, a voltage-gated 'muscle-type' chloride channel, the functional complex is known to be a homo-oligomer of a polypeptide of Mr approximately 90,000, with no associated 'helper' subunits. The subunit stoichiometry of ClC-type channels is controversial, however, with either dimeric or tetrameric association suggested by different indirect experiments. Before a coherent molecular view of this new class of ion channels can emerge, the fundamental question of subunit composition must first be settled. We have examined hybrid ClC-0 channels constructed from functionally tagged subunits, and report here that ClC-0 is a homodimer containing two chloride-conduction pores.