Gating the Selectivity Filter in ClC Chloride Channels.

IONS; MUSCLE cells; BODY fluids; NERVOUS system; CELL membranes; PHYSIOLOGICAL control systems

CIC channels conduct chloride (Cl[sup−]) ions across cell membranes and thereby govern the electrical activity of muscle cells and certain neurons, the transport of fluid and electrolytes across epithelia, and the acidification of intracellular vesicles. The structural basis of CIC channel gating was studied. Crystal structures of wild-type and mutant Escherichia coli CIC channels bound to a monoclonal Fab fragment reveal three Cl[sup−] binding sites within the 15-angstrom neck of an hourglass-shaped pore. The Cl[sup−] binding site nearest the extracellular solution can be occupied either by a Cl[sup−] ion or by a glutamate carboxyl group. Mutations of this glutamate residue in Torpedo ray CIC 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[sup−] ion. [ABSTRACT FROM AUTHOR]

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