ArticleThe Journal of general physiology2003
Side-chain charge effects and conductance determinants in the pore of ClC-0 chloride channels.
Article in The Journal of general physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- Biophysical and Pharmacological Insights to CLC Chloride Channels.Handbook of experimental pharmacology · 2024Article
- Cryo-EM structures of the TTYH family reveal a novel architecture for lipid interactions.Nature communications · 2021Article
- 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
- Comparison of ion transport determinants between a TMEM16 chloride channel and phospholipid scramblase.The Journal of general physiology · 2019Article
- Independent activation of ion conduction pores in the double-barreled calcium-activated chloride channel TMEM16A.The Journal of general physiology · 2016Article
- Independent activation of distinct pores in dimeric TMEM16A channels.The Journal of general physiology · 2016Article
- Structure and gating of CLC channels and exchangers.The Journal of physiology · 2015Review
- Regulatory phosphorylation induces extracellular conformational changes in a CLC anion channel.Biophysical journal · 2013Article
- Molecular mechanism of proton transport in CLC Cl-/H+ exchange transporters.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Influences of mutations on the electrostatic binding free energies of chloride ions in Escherichia coli ClC.The journal of physical chemistry. B · 2012Article
- Synergistic substrate binding determines the stoichiometry of transport of a prokaryotic H(+)/Cl(-) exchanger.Nature structural & molecular biology · 2012Article
- Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle.Science (New York, N.Y.) · 2010Article
- CLC channels and transporters: proteins with borderline personalities.Biochimica et biophysica acta · 2010Review
- A three-state multi-ion kinetic model for conduction properties of ClC-0 chloride channel.Biophysical journal · 2010Article
- Accessibility of the CLC-0 pore to charged methanethiosulfonate reagents.Biophysical journal · 2010Article
- Proton transport pathway in the ClC Cl-/H+ antiporter.Biophysical journal · 2009Article
- Review. Proton-coupled gating in chloride channels.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2009Review
- Blocking pore-open mutants of CLC-0 by amphiphilic blockers.The Journal of general physiology · 2009Article
- Ion permeation through a Cl--selective channel designed from a CLC Cl-/H+ exchanger.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
The charge on the side chain of the internal pore residue lysine 519 (K519) of the Torpedo ClC-0 chloride (Cl-) channel affects channel conductance. Experiments that replace wild-type (WT) lysine with neutral or negatively charged residues or that modify the K519C mutant with various methane thiosulfonate (MTS) reagents show that the conductance of the channel decreases when the charge at position 519 is made more negative. This charge effect on the channel conductance diminishes in the presence of a high intracellular Cl- concentration ([Cl-]i). However, the application of high concentrations of nonpermeant ions, such as glutamate or sulfate (SO42-), does not change the conductance, suggesting that the electrostatic effects created by the charge at position 519 are unlikely due to a surface charge mechanism. Another pore residue, glutamate 127 (E127), plays an even more critical role in controlling channel conductance. This negatively charged residue, based on the structures of the homologous bacterial ClC channels, lies 4-5 A from K519. Altering the charge of this residue can influence the apparent Cl- affinity as well as the saturated pore conductance in the conductance-Cl- activity curve. Amino acid residues at the selectivity filter also control the pore conductance but mutating these residues mainly affects the maximal pore conductance. These results suggest at least two different conductance determinants in the pore of ClC-0, consistent with the most recent crystal structure of the bacterial ClC channel solved to 2.5 A, in which multiple Cl--binding sites were identified in the pore. Thus, we suggest that the occupancy of the internal Cl--binding site is directly controlled by the charged residues located at the inner pore mouth. On the other hand, the Cl--binding site at the selectivity filter controls the exit rate of Cl- and therefore determines the maximal channel conductance.
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