ArticlePLoS computational biology2012
Molecular mechanism for the dual alcohol modulation of Cys-loop receptors.
Article in PLoS computational biology, 2012. 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, 37 citations in OpenAlex.
- Single nucleotide variants inBiochemistry and biophysics reports · 2026Article
- Molecular Imaging Studies of Alcohol Use Disorder.Current topics in behavioral neurosciences · 2025Review
- Simulation and Machine Learning Methods for Ion-Channel Structure Determination, Mechanistic Studies and Drug Design.Frontiers in pharmacology · 2022Review
- Markov state models of proton- and pore-dependent activation in a pentameric ligand-gated ion channel.eLife · 2021Article
- Effect of ethanol on Munc13-1 C1 in Membrane: A Molecular Dynamics Simulation Study.Alcoholism, clinical and experimental research · 2020Article
- Mutagenesis computer experiments in pentameric ligand-gated ion channels: the role of simulation tools with different resolution.Interface focus · 2019Review
- The intriguing effect of ethanol and nicotine on acetylcholine-sensitive potassium current IKAch: Insight from a quantitative model.PloS one · 2019Article
- Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.Biochimica et biophysica acta. Biomembranes · 2018Review
- Molecular basis for potentiation of Cx36 gap junction channel conductance byBioscience reports · 2018Article
- Mapping two neurosteroid-modulatory sites in the prototypic pentameric ligand-gated ion channel GLIC.The Journal of biological chemistry · 2018Article
- Inward rectifying potassium currents resolved into components: modeling of complex drug actions.Pflugers Archiv : European journal of physiology · 2018Article
- Alcohol reduces muscle fatigue through atomistic interactions with nicotinic receptors.Communications biology · 2018Article
- Article
- A membrane-embedded pathway delivers general anesthetics to two interacting binding sites in theThe Journal of biological chemistry · 2017Article
- Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- The cellular membrane as a mediator for small molecule interaction with membrane proteins.Biochimica et biophysica acta · 2016Article
- Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine.Naunyn-Schmiedeberg's archives of pharmacology · 2016Article
- Identification of an Inhibitory Alcohol Binding Site in GABAA ρ1 Receptors.ACS chemical neuroscience · 2016Article
- Inter- and Intra-Subunit Butanol/Isoflurane Sites of Action in the Human Glycine Receptor.Frontiers in molecular neuroscience · 2016Article
- Evidence for α-helices in the large intracellular domain mediating modulation of the α1-glycine receptor by ethanol and Gβγ.The Journal of pharmacology and experimental therapeutics · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Cys-loop receptors constitute a superfamily of pentameric ligand-gated ion channels (pLGICs), including receptors for acetylcholine, serotonin, glycine and γ-aminobutyric acid. Several bacterial homologues have been identified that are excellent models for understanding allosteric binding of alcohols and anesthetics in human Cys-loop receptors. Recently, we showed that a single point mutation on a prokaryotic homologue (GLIC) could transform it from a channel weakly potentiated by ethanol into a highly ethanol-sensitive channel. Here, we have employed molecular simulations to study ethanol binding to GLIC, and to elucidate the role of the ethanol-enhancing mutation in GLIC modulation. By performing 1-µs simulations with and without ethanol on wild-type and mutated GLIC, we observed spontaneous binding in both intra-subunit and inter-subunit transmembrane cavities. In contrast to the glycine receptor GlyR, in which we previously observed ethanol binding primarily in an inter-subunit cavity, ethanol primarily occupied an intra-subunit cavity in wild-type GLIC. However, the highly ethanol-sensitive GLIC mutation significantly enhanced ethanol binding in the inter-subunit cavity. These results demonstrate dramatic effects of the F(14')A mutation on the distribution of ligands, and are consistent with a two-site model of pLGIC inhibition and potentiation.
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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.