CLC chloride channels: correlating structure with function

Abstract

CLC chloride channels form a large gene family that is found in bacteria, archae and eukaryotes. Previous mutagenesis studies on CLC chloride channels, combined with electrophysiology, strongly supported the theory that these channels form a homodimeric structure with one pore per subunit (a'double-barrelled' channel), and also provided clues about gating and permeation. Recently, the crystal structures of two bacterial CLC proteins have been obtained by X-ray diffraction analysis. They confirm the double-barrelled architecture, and reveal a surprisingly complex and unprecedented channel structure. At its binding site in the pore, chloride interacts with the ends of four helices that come from both sides of the membrane. A glutamate residue that protrudes into the pore is proposed to participate in gating. The structure confirms several previous conclusions from mutagenesis studies and provides an excellent framework for their interpretation.