Projection structure of a CIC-type chloride channel at 6.5 angstrom resolution

Virtually all cells in all eukaryotic organisms express ion channels of the ClC type, the only known molecular family of chloride-ion-selective channe ls. The diversity of ClC channels highlights the multitude and range of fun ctions served by gated chloride-ion conduction in biological membranes, suc h as controlling electrical excitability in skeletal muscle, maintaining sy stemic blood pressure, acidifying endosomal compartments, and regulating el ectrical responses of GABA (gamma -aminobutyric acid)-containing interneuro ns in the central nervous system(1). Previously, we expressed and purified a prokaryotic ClC channel homologue(2). Here we report the formation of two -dimensional crystals of this ClC channel protein reconstituted into phosph olipid bilayer membranes. Cryo-electron microscopic analysis of these cryst als yields a projection structure at 6.5 Angstrom resolution, which shows o ff-axis water-filled pores within the dimeric channel complex.