ArticleeLife2016
Revealing an outward-facing open conformational state in a CLC Cl(-)/H(+) exchange transporter.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Molecular mechanism of exchange coupling in CLC chloride/proton antiporters.Nature communications · 2026Article
- A large-scale evolutionary and structural analysis of CLC channels and transporters.Protein science : a publication of the Protein Society · 2025Article
- Molecular simulations meet personalized medicine: The mechanism of action of CLC-5 antiporter and the origin of Dent's disease.PNAS nexus · 2025Article
- Article
- 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
- Molecular basis of ClC-6 function and its impairment in human disease.Science advances · 2023Article
- The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter.Biophysical journal · 2023Article
- 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
- Localization atomic force microscopy.Nature · 2021Article
- Altering CLC stoichiometry by reducing non-polar side-chains at the dimerization interface.Journal of molecular biology · 2021Article
- Q-cubed mutant cues clues to CLC antiport mechanism.The Journal of general physiology · 2021Article
- Divergent CleLife · 2020Article
- A CLC-ec1 mutant reveals global conformational change and suggests a unifying mechanism for the CLC CleLife · 2020Article
- Local conformational dynamics regulating transport properties of a ClJournal of computational chemistry · 2020Article
- Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating.PLoS computational biology · 2020Article
- Mutation of external glutamate residue reveals a new intermediate transport state and anion binding site in a CLC ClProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Structure of the human ClC-1 chloride channel.PLoS biology · 2019Article
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Authors and funding
13 authors.
Funding
Abstract
CLC secondary active transporters exchange Cl(-) for H(+). Crystal structures have suggested that the conformational change from occluded to outward-facing states is unusually simple, involving only the rotation of a conserved glutamate (Gluex) upon its protonation. Using (19)F NMR, we show that as [H(+)] is increased to protonate Gluex and enrich the outward-facing state, a residue ~20 Å away from Gluex, near the subunit interface, moves from buried to solvent-exposed. Consistent with functional relevance of this motion, constriction via inter-subunit cross-linking reduces transport. Molecular dynamics simulations indicate that the cross-link dampens extracellular gate-opening motions. In support of this model, mutations that decrease steric contact between Helix N (part of the extracellular gate) and Helix P (at the subunit interface) remove the inhibitory effect of the cross-link. Together, these results demonstrate the formation of a previously uncharacterized 'outward-facing open' state, and highlight the relevance of global structural changes in CLC function.
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