ArticleBiophysical journal2012
Molecular dynamics investigation of Cl- and water transport through a eukaryotic CLC transporter.
Article in Biophysical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Structural insights into anion selectivity and activation mechanism of LRRC8 volume-regulated anion channels.Cell reports · 2023Article
- Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating.PLoS computational biology · 2020Article
- Multiscale Kinetic Modeling Reveals an Ensemble of ClJournal of the American Chemical Society · 2018Article
- 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
- Identification of New Shikonin Derivatives as Antitumor Agents Targeting STAT3 SH2 Domain.Scientific reports · 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
- Computational characterization of structural dynamics underlying function in active membrane transporters.Current opinion in structural biology · 2015Review
- 13C NMR detects conformational change in the 100-kD membrane transporter ClC-ec1.Journal of biomolecular NMR · 2015Article
- P-loop conformation governed crizotinib resistance in G2032R-mutated ROS1 tyrosine kinase: clues from free energy landscape.PLoS computational biology · 2014Article
- Coupling between neurotransmitter translocation and protonation state of a titratable residue during Na ⁺-coupled transport.Biophysical journal · 2014Article
- Water access points and hydration pathways in CLC H+/Cl- transporters.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Prerequisites to proton transport in the bacterial ClC-ec1 Cl-/H+ exchanger.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Modeling and simulation of ion channels.Chemical reviews · 2012Review
- Intracellular proton access in a Cl(-)/H(+) antiporter.PLoS biology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early crystal structures of prokaryotic CLC proteins identified three Cl(-) binding sites: internal (S(int)), central (S(cen)), and external (S(ext)). A conserved external GLU (GLU(ex)) residue acts as a gate competing for S(ext). Recently, the first crystal structure of a eukaryotic transporter, CmCLC, revealed that in this transporter GLU(ex) competes instead for S(cen). Here, we use molecular dynamics simulations to investigate Cl(-) transport through CmCLC. The gating and Cl(-)/H(+) transport cycle are inferred through comparative molecular dynamics simulations with protonated and deprotonated GLU(ex) in the presence/absence of external potentials. Adaptive biasing force calculations are employed to estimate the potential of mean force profiles associated with transport of a Cl(-) ion from S(ext) to S(int), depending on the Cl(-) occupancy of other sites. Our simulations demonstrate that protonation of GLU(ex) is essential for Cl(-) transport from S(ext) to S(cen). The S(cen) site may be occupied by two Cl(-) ions simultaneously due to a high energy barrier (∼8 Kcal/mol) for a single Cl(-) ion to translocate from S(cen) to S(int). Binding two Cl(-) ions to S(cen) induces a continuous water wire from S(cen) to the extracellular solution through the side chain of the GLU(ex) gate. This may initiate deprotonation of GLU(ex), which then drives the two Cl(-) ions out of S(cen) toward the intracellular side via two putative Cl(-) transport paths. Finally, a conformational cycle is proposed that would account for the exchange stoichiometry.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.