ArticlePLoS biology2019
Structure of the human ClC-1 chloride channel.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.Journal of neuromuscular diseases · 2021Pooled it
- DM: a simple solution to suppress air-water interface interactions in cryo-EM.bioRxiv : the preprint server for biology · 2026Article
- Genome-wide identification, expression and evolutionary analysis of the CLC gene family in Vigna radiata L. reveals its roles in salt resistance.BMC genomics · 2025Article
- Molecular simulations meet personalized medicine: The mechanism of action of CLC-5 antiporter and the origin of Dent's disease.PNAS nexus · 2025Article
- Pleiotropic Effects of the NSAID Fenamates on Chloride Channels: Opportunity for Ion Channelopathies?Pharmacology research & perspectives · 2025Review
- ALLIN: A tool for annotation of a protein alignment combined with structural visualization.The Journal of general physiology · 2025Article
- Article
- Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger.Nature communications · 2024Article
- Cryo-EM structures of the human band 3 transporter indicate a transport mechanism involving the coupled movement of chloride and bicarbonate ions.PLoS biology · 2024Article
- Insights into CLC-0's Slow-Gating from Intracellular Proton Inhibition.International journal of molecular sciences · 2024Article
- CryoEM grid preparation: a closer look at advancements and impact of preparation mode and new approaches.Biochemical Society transactions · 2024Review
- Article
- ClC-K Kidney Chloride Channels: From Structure to Pathology.Handbook of experimental pharmacology · 2024Article
- Biophysical and Pharmacological Insights to CLC Chloride Channels.Handbook of experimental pharmacology · 2024Article
- The Role of Chloride Channels in Plant Responses to NaCl.International journal of molecular sciences · 2023Review
- 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
- Molecular basis of ClC-6 function and its impairment in human disease.Science advances · 2023Article
- ClC-1 Chloride Channel: Inputs on the Structure-Function Relationship of Myotonia Congenita-Causing Mutations.Biomedicines · 2023Review
- Theoretical framework and experimental solution for the air-water interface adsorption problem in cryoEM.Biophysics reports · 2023Article
- Molecular mechanism underlying regulation of Arabidopsis CLCa transporter by nucleotides and phospholipids.Nature communications · 2023Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
ClC-1 protein channels facilitate rapid passage of chloride ions across cellular membranes, thereby orchestrating skeletal muscle excitability. Malfunction of ClC-1 is associated with myotonia congenita, a disease impairing muscle relaxation. Here, we present the cryo-electron microscopy (cryo-EM) structure of human ClC-1, uncovering an architecture reminiscent of that of bovine ClC-K and CLC transporters. The chloride conducting pathway exhibits distinct features, including a central glutamate residue ("fast gate") known to confer voltage-dependence (a mechanistic feature not present in ClC-K), linked to a somewhat rearranged central tyrosine and a narrower aperture of the pore toward the extracellular vestibule. These characteristics agree with the lower chloride flux of ClC-1 compared with ClC-K and enable us to propose a model for chloride passage in voltage-dependent CLC channels. Comparison of structures derived from protein studied in different experimental conditions supports the notion that pH and adenine nucleotides regulate ClC-1 through interactions between the so-called cystathionine-β-synthase (CBS) domains and the intracellular vestibule ("slow gating"). The structure also provides a framework for analysis of mutations causing myotonia congenita and reveals a striking correlation between mutated residues and the phenotypic effect on voltage gating, opening avenues for rational design of therapies against ClC-1-related diseases.
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Registered trials
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