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Molecular mechanism of proton transport in CLC Cl - /H + exchange transporters

Feng, Liang, Campbell, Ernest B., MacKinnon, Roderick·2012·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1205764109
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Abstract

CLC proteins underlie muscle, kidney, bone, and other organ system function by catalyzing the transport of Cl - ions across cell and organellar membranes. Some CLC proteins are ion channels while others are pumps that exchange Cl - for H + . The pathway through which Cl - ions cross the membrane has been characterized, but the transport of H + and the principle by which their movement is coupled to Cl - movement is not well understood. Here we show that H + transport depends not only on the presence of a specific glutamate residue but also the presence of Cl - ions. H + transport, however, can be isolated and analyzed in the absence of Cl - by mutating the glutamate to alanine and adding carboxylate-containing molecules to solution, consistent with the notion that H + transfer is mediated through the entry of a carboxylate group into the anion pathway. Cl - ions and carboxylate interact with each other strongly. These data support a mechanism in which the glutamate carboxylate functions as a surrogate Cl - ion, but it can accept a H + and transfer it between the external solution and the central Cl - binding site, coupled to the movement of 2 Cl - ions.

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Metadata

Authors
Feng, L., Campbell, E. B., & MacKinnon, R.
Affiliations
Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2012-07-02
Volume
109
Issue
29
Pages
11699-11704
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.1205764109
Cited by
82
References
1
Language
en

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CoChat. (2026). Citation check: Molecular mechanism of proton transport in CLC Cl - /H + exchange transporters. https://app.cochat.ai/papers/10.1073/pnas.1205764109
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Feng, L., Campbell, E. B., & MacKinnon, R. (2012). Molecular mechanism of proton transport in CLC Cl - /H + exchange transporters. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1205764109