ArticleThe Journal of general physiology2005
Separate ion pathways in a Cl-/H+ exchanger.
Article in The Journal of general physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 208 citations in OpenAlex.
- Molecular mechanism of exchange coupling in CLC chloride/proton antiporters.Nature communications · 2026Article
- Secreting salt glands constrain cuticle fracture to enhance desalination efficiency.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7.bioRxiv : the preprint server for biology · 2025Article
- Endosomal chloride/proton exchangers need inhibitory TMEM9 β-subunits for regulation and prevention of disease-causing overactivity.Nature communications · 2025Article
- Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger.Nature communications · 2024Article
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Fluoride Transport and Inhibition Across CLC Transporters.Handbook of experimental pharmacology · 2024Article
- The Role of Chloride Channels in Plant Responses to NaCl.International journal of molecular sciences · 2023Review
- Membrane defects as a generalized driving force for membrane protein interactions.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Molecular basis of ClC-6 function and its impairment in human disease.Science advances · 2023Article
- Molecular mechanism underlying regulation of Arabidopsis CLCa transporter by nucleotides and phospholipids.Nature communications · 2023Article
- ClC Chloride Channels in Gram-Negative Bacteria and Its Role in the Acid Resistance Systems.Journal of microbiology and biotechnology · 2023Review
- The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter.Biophysical journal · 2023Article
- Chloride Channel Family in the EuhalophyteInternational journal of molecular sciences · 2023Article
- Molecular Cloning and Characterization of SaCLCd, SaCLCf, and SaCLCg, Novel Proteins of the Chloride Channel Family (CLC) from the HalophytePlants (Basel, Switzerland) · 2022Article
- The Role of the Lysosomal ClCells · 2022Review
- ClC-3 regulates the excitability of nociceptive neurons and is involved in inflammatory processes within the spinal sensory pathway.Frontiers in cellular neuroscience · 2022Article
- Simulation of pH-Dependent Conformational Transitions in Membrane Proteins: The CLC-ec1 ClMolecules (Basel, Switzerland) · 2021Article
- Toward a Multipathway Perspective: pH-Dependent Kinetic Selection of Competing Pathways and the Role of the Internal Glutamate in ClThe journal of physical chemistry. B · 2021Article
- Electro-steric opening of the CLC-2 chloride channel gate.Scientific reports · 2021Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
CLC-ec1 is a prokaryotic CLC-type Cl(-)/H+ exchange transporter. Little is known about the mechanism of H+ coupling to Cl-. A critical glutamate residue, E148, was previously shown to be required for Cl(-)/H+ exchange by mediating proton transfer between the protein and the extracellular solution. To test whether an analogous H+ acceptor exists near the intracellular side of the protein, we performed a mutagenesis scan of inward-facing carboxyl-bearing residues and identified E203 as the unique residue whose neutralization abolishes H+ coupling to Cl- transport. Glutamate at this position is strictly conserved in all known CLCs of the transporter subclass, while valine is always found here in CLC channels. The x-ray crystal structure of the E203Q mutant is similar to that of the wild-type protein. Cl- transport rate in E203Q is inhibited at neutral pH, and the double mutant, E148A/E203Q, shows maximal Cl- transport, independent of pH, as does the single mutant E148A. The results argue that substrate exchange by CLC-ec1 involves two separate but partially overlapping permeation pathways, one for Cl- and one for H+. These pathways are congruent from the protein's extracellular surface to E148, and they diverge beyond this point toward the intracellular side. This picture demands a transport mechanism fundamentally different from familiar alternating-access schemes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.