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Homodimeric architecture of a CIC-type chloride ion channel

Abstract

THE recent discovery of the CIC-family of anion-conducting channel proteins1–3 has led to an appreciation of the central roles played by chloride ion channels in cellular functions, such as electrical behaviour of muscle4–7 and nerve8 and epithelial solute transport9. Little is known, however, about molecular architecture or sequence–function relationships in these membrane proteins. In the single case of C1C-0, a voltage-gated 'muscle-type' chloride channel, the functional complex is known to be a homo-oligomer of a polypeptide of Mr ˜ 90,000, with no associated 'helper' summits10. The subunit stoichiometry of CIC-type channels is controversial, however, with either dimeric or tetrameric association suggested by different indirect experi-ments10,11. 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 C1C-0 channels constructed from functionally tagged subunits, and report here that C1C-0 is a homodimer containing two chloride-conduction pores.

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Middleton, R., Pheasant, D. & Miller, C. Homodimeric architecture of a CIC-type chloride ion channel. Nature 383, 337–340 (1996). https://doi.org/10.1038/383337a0

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