ArticleProceedings of the National Academy of Sciences of the United States of America2012
Molecular mechanism of proton transport in CLC Cl-/H+ exchange transporters.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Identification, expression and potential functional analyses of the seven chloride channels in grapevine.Protoplasma · 2026Article
- Multiscale Responsive Kinetic Modeling: Quantifying Biomolecular Reaction Flux under Varying Electrochemical Conditions.Journal of chemical theory and computation · 2025Article
- Multiscale Responsive Kinetic Modeling: Quantifying Biomolecular Reaction Flux under Varying Electrochemical Conditions.bioRxiv : the preprint server for biology · 2024Article
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Structural identification of a selectivity filter in CFTR.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Biophysical and Pharmacological Insights to CLC Chloride Channels.Handbook of experimental pharmacology · 2024Article
- CryoEM structures of the human CLC-2 voltage gated chloride channel reveal a ball and chain gating mechanism.bioRxiv : the preprint server for biology · 2023Article
- Atomic structure of the open SARS-CoV-2 E viroporin.Science advances · 2023Article
- Molecular basis of ClC-6 function and its impairment in human disease.Science advances · 2023Article
- ClC Chloride Channels in Gram-Negative Bacteria and Its Role in the Acid Resistance Systems.Journal of microbiology and biotechnology · 2023Review
- Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42.Nature communications · 2023Article
- The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter.Biophysical journal · 2023Article
- Review
- Vesicular CLC chloride/proton exchangers in health and diseases.Frontiers in pharmacology · 2023Review
- Article
- Article
- The Role of the Lysosomal ClCells · 2022Review
- Review
- Article
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Authors and funding
3 authors.
Funding
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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