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X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity

Dutzler, Raimund, Campbell, Ernest B., Cadene, Martine, Chait, Brian T., MacKinnon, Roderick·2002·Nature
DOI 10.1038/415287a
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Abstract

The ClC chloride channels catalyse the selective flow of Cl- ions across cell membranes, thereby regulating electrical excitation in skeletal muscle and the flow of salt and water across epithelial barriers. Genetic defects in ClC Cl- channels underlie several familial muscle and kidney diseases. Here we present the X-ray structures of two prokaryotic ClC Cl- channels from Salmonella enterica serovar typhimurium and Escherichia coli at 3.0 and 3.5 A, respectively. Both structures reveal two identical pores, each pore being formed by a separate subunit contained within a homodimeric membrane protein. Individual subunits are composed of two roughly repeated halves that span the membrane with opposite orientations. This antiparallel architecture defines a selectivity filter in which a Cl- ion is stabilized by electrostatic interactions with alpha-helix dipoles and by chemical coordination with nitrogen atoms and hydroxyl groups. These findings provide a structural basis for further understanding the function of ClC Cl- channels, and establish the physical and chemical basis of their anion selectivity.

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  • A number of Cl− transporting CLCs have been structurally characterized, providing a deep mechanistic basis for understanding the fluoride riboswitch-associated CLCs.

    “A number of Cl− transporting CLCs have been structurally characterized, providing a deep mechanistic basis for understanding the fluoride riboswitch-associated CLCs (42–46).”

    From Membrane exporters of fluoride ion (2021) · cites this paper as [42]

  • A sidechain hydroxyl from Y396 coordinates the fluoride, an interaction with precedent in Cl− transporters.

    “In an interaction that has precedent in the Cl− transporters (42), a sidechain hydroxyl from Y396 coordinates the fluoride.”

    From Membrane exporters of fluoride ion (2021) · cites this paper as [42]

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Metadata

Authors
Dutzler, R., Campbell, E. B., Cadene, M., Chait, B. T., & MacKinnon, R.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2002-01
Volume
415
Issue
6869
Pages
287-294
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/415287a
Cited by
1,446
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

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