Structural basis for ion conduction and gating in ClC chloride channels

FEBS Letters

Dutzler, Raimund¹ 

[1] Department of Biochemistry, University of Zurich, Winterthurerstr. 190, CH-8057 Zurich, Switzerland

关键词: Chloride channel;    Chloride selectivity;    Gating;   

DOI  :  10.1016/S0014-5793(04)00210-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Members of the ClC family of voltage-gated chloride channels are found from bacteria to mammals with a considerable degree of conservation in the membrane-inserted, pore-forming region. The crystal structures of the ClC channels of Escherichia coli and Salmonella typhimurium provide a structural framework for the entire family. The ClC channels are homodimeric proteins with an overall rhombus-like shape. Each ClC dimer has two pores each contained within a single subunit. The ClC subunit consists of two roughly repeated halves that span the membrane with opposite orientations. This antiparallel architecture defines a chloride selectivity filter within the 15-Å neck of a hourglass-shaped pore. Three Cl⁻ binding sites within the selectivity filter stabilize ions by interactions with α-helix dipoles and by chemical interactions with nitrogen atoms and hydroxyl groups of residues in the protein. The Cl⁻ binding site nearest the extracellular solution can be occupied either by a Cl⁻ ion or by a glutamate carboxyl group. Mutations of this glutamate residue in Torpedo ray ClC channels alter gating in electrophysiological assays. These findings reveal a form of gating in which the glutamate carboxyl group closes the pore by mimicking a Cl⁻ ion.

【 授权许可】

Unknown