Gating the selectivity filter in ClC chloride channels

Raimund Dutzler; Ernest B Campbell; Roderick MacKinnon

doi:10.1126/science.1082708

Gating the selectivity filter in ClC chloride channels

Science. 2003 Apr 4;300(5616):108-12. doi: 10.1126/science.1082708. Epub 2003 Mar 20.

Authors

Raimund Dutzler¹, Ernest B Campbell, Roderick MacKinnon

Affiliation

¹ Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

PMID: 12649487
DOI: 10.1126/science.1082708

Abstract

ClC channels conduct chloride (Cl-) 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 ClC channel gating was studied. Crystal structures of wild-type and mutant Escherichia coli ClC channels bound to a monoclonal Fab fragment reveal three Cl- binding sites within the 15-angstrom neck of an hourglass-shaped pore. 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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Acid Substitution
Animals
Antibodies, Monoclonal / immunology
Binding Sites
Chloride Channels / chemistry*
Chloride Channels / genetics
Chloride Channels / immunology
Chloride Channels / physiology*
Chlorides / metabolism*
Crystallography, X-Ray
Dimerization
Escherichia coli / chemistry
Escherichia coli / metabolism
Escherichia coli Proteins / chemistry
Escherichia coli Proteins / genetics
Escherichia coli Proteins / immunology
Escherichia coli Proteins / metabolism
Glutamates / chemistry
Glutamates / metabolism
Hydrogen Bonding
Hydrogen-Ion Concentration
Immunoglobulin Fab Fragments / immunology
Ion Channel Gating*
Models, Molecular
Oocytes
Patch-Clamp Techniques
Point Mutation
Protein Conformation
Protein Structure, Secondary
Protein Structure, Tertiary
Torpedo
Xenopus

Substances

Antibodies, Monoclonal
CLC-0 chloride channel protein, Torpedo californica
Chloride Channels
Chlorides
Escherichia coli Proteins
Glutamates
Immunoglobulin Fab Fragments

Associated data

PDB/10TS
PDB/10TT
PDB/10TU