ArticleBiophysical journal2014
A predicted binding site for cholesterol on the GABAA receptor.
Article in Biophysical journal, 2014. 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.
- GABA and astrocytic cholesterol determine the lipid environment of GABACommunications biology · 2025Article
- Transcriptional Dysregulation of Cholesterol Synthesis Underlies Hyposensitivity to GABA in the Ventral Tegmental Area During Acute Alcohol Withdrawal.Biological psychiatry · 2024Article
- Structure-function Studies of GABA (A) Receptors and Related computer-aided Studies.Journal of molecular neuroscience : MN · 2023Review
- Molecular Biophysics of Class A G Protein Coupled Receptors-Lipids Interactome at a Glance-Highlights from the ABiomolecules · 2023Review
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Cholesterol-induced suppression of Kir2 channels is mediated by decoupling at the inter-subunit interfaces.iScience · 2022Article
- Fluorescence microscopy imaging of a neurotransmitter receptor and its cell membrane lipid milieu.Frontiers in molecular biosciences · 2022Review
- Interfacial binding sites for cholesterol on GABABiophysical journal · 2021Article
- Tracking Membrane Protein Dynamics in Real Time.The Journal of membrane biology · 2021Review
- State-dependent protein-lipid interactions of a pentameric ligand-gated ion channel in a neuronal membrane.PLoS computational biology · 2021Article
- Druggable Lipid Binding Sites in Pentameric Ligand-Gated Ion Channels and Transient Receptor Potential Channels.Frontiers in physiology · 2021Review
- Dysregulation of Neuronal Nicotinic Acetylcholine Receptor-Cholesterol Crosstalk in Autism Spectrum Disorder.Frontiers in molecular neuroscience · 2021Article
- Thermophoretic analysis of ligand-specific conformational states of the inhibitory glycine receptor embedded in copolymer nanodiscs.Scientific reports · 2020Article
- Functional marriage in plasma membrane: Critical cholesterol level-optimal protein activity.British journal of pharmacology · 2020Review
- Microsecond-timescale simulations suggest 5-HT-mediated preactivation of the 5-HTProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Comparative docking analysis of cholesterol analogs to ion channels to discriminate between stereospecific binding vs. stereospecific response.Channels (Austin, Tex.) · 2019Article
- Untangling Direct and Domain-Mediated Interactions Between Nicotinic Acetylcholine Receptors in DHA-Rich Membranes.The Journal of membrane biology · 2019Article
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Modulation of the GABA type A receptor (GABAAR) function by cholesterol and other steroids is documented at the functional level, yet its structural basis is largely unknown. Current data on structurally related modulators suggest that cholesterol binds to subunit interfaces between transmembrane domains of the GABAAR. We construct homology models of a human GABAAR based on the structure of the glutamate-gated chloride channel GluCl of Caenorhabditis elegans. The models show the possibility of previously unreported disulfide bridges linking the M1 and M3 transmembrane helices in the α and γ subunits. We discuss the biological relevance of such disulfide bridges. Using our models, we investigate cholesterol binding to intersubunit cavities of the GABAAR transmembrane domain. We find that very similar binding modes are predicted independently by three approaches: analogy with ivermectin in the GluCl crystal structure, automated docking by AutoDock, and spontaneous rebinding events in unbiased molecular dynamics simulations. Taken together, the models and atomistic simulations suggest a somewhat flexible binding mode, with several possible orientations. Finally, we explore the possibility that cholesterol promotes pore opening through a wedge mechanism.
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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.