ArticleBiophysical journal2004
Exterior site occupancy infers chloride-induced proton gating in a prokaryotic homolog of the ClC chloride channel.
Article in Biophysical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 58 citations in OpenAlex.
- Start Me Up: How Can Surrounding Gangliosides Affect Sodium-Potassium ATPase Activity and Steer towards Pathological Ion Imbalance in Neurons?Biomedicines · 2022Review
- Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating.PLoS computational biology · 2020Article
- Chloride Ion Transport by theFrontiers in chemistry · 2018Article
- Two Cl Ions and a Glu Compete for a Helix Cage in the CLC Proton/ClBiophysical journal · 2017Article
- Multiscale Simulations Reveal Key Aspects of the Proton Transport Mechanism in the ClC-ec1 Antiporter.Biophysical journal · 2016Article
- Molecular Basis for Differential Anion Binding and Proton Coupling in the Cl(-)/H(+) Exchanger ClC-ec1.Journal of the American Chemical Society · 2016Article
- Revealing an outward-facing open conformational state in a CLC Cl(-)/H(+) exchange transporter.eLife · 2016Article
- Identification of the antiepileptic racetam binding site in the synaptic vesicle protein 2A by molecular dynamics and docking simulations.Frontiers in cellular neuroscience · 2015Article
- Partial least-squares functional mode analysis: application to the membrane proteins AQP1, Aqy1, and CLC-ec1.Biophysical journal · 2012Article
- Influences of mutations on the electrostatic binding free energies of chloride ions in Escherichia coli ClC.The journal of physical chemistry. B · 2012Article
- Molecular dynamics investigation of Cl- and water transport through a eukaryotic CLC transporter.Biophysical journal · 2012Article
- The coupled proton transport in the ClC-ec1 Cl(-)/H(+) antiporter.Biophysical journal · 2011Article
- A three-state multi-ion kinetic model for conduction properties of ClC-0 chloride channel.Biophysical journal · 2010Article
- Permeant anions contribute to voltage dependence of ClC-2 chloride channel by interacting with the protopore gate.The Journal of physiology · 2010Article
- Secondary water pore formation for proton transport in a ClC exchanger revealed by an atomistic molecular-dynamics simulation.Biophysical journal · 2010Article
- Proton transport pathway in the ClC Cl-/H+ antiporter.Biophysical journal · 2009Article
- Statistical determinants of selective ionic complexation: ions in solvent, transport proteins, and other "hosts".Biophysical journal · 2009Article
- The role of a conserved lysine in chloride- and voltage-dependent ClC-0 fast gating.The Journal of general physiology · 2007Article
- The mechanism of fast-gate opening in ClC-0.The Journal of general physiology · 2007Article
- Roles of K149, G352, and H401 in the channel functions of ClC-0: testing the predictions from theoretical calculations.The Journal of general physiology · 2006Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The ClC family of anion channels mediates the efficient, selective permeation of Cl(-) across the biological membranes of living cells under the driving force of an electrochemical gradient. In some eukaryotes, these channels are known to exhibit a unique gating mechanism, which appears to be triggered by the permeant Cl(-) anion. We infer details of this gating mechanism by studying the free energetics of Cl(-) occupancy in the pore of a prokaryotic ClC homolog. These free energetics were gleaned from 30 ns of molecular dynamics simulation on an approximately 133,000-atom system consisting of a hydrated membrane embedded StClC transporter. The binding sites for Cl(-) in the transporter were determined for the cases where the putative gating residue, Glu(148), was protonated and unprotonated. When the glutamate gate is protonated, Cl(-) favorably occupies an exterior site, S(ext), to form a queue of anions in the pore. However, when the glutamate gate is unprotonated, Cl(-) cannot occupy this site nor, consequently, pass through the pore. An additional, previously undetected, site was found in the pore near the outer membrane that exists regardless of the protonation state of Glu(148). Although this suggests that, for the prokaryotic homolog, protonation of Glu(148) may be the first step in transporting Cl(-) at the expense of H(+) transport in the opposite direction, an evolutionary argument might suggest that Cl(-) opens the ClC gate in eukaryotic channels by inducing the conserved glutamate's protonation. During an additional 20 ns free dynamics simulation, the newly discovered outermost site, S(out), and the innermost site, S(int), were seen to allow spontaneous exchange of Cl(-) ions with the bulk electrolyte while under depolarization conditions.
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