ArticleThe Journal of biological chemistry2021
Regulation of a pentameric ligand-gated ion channel by a semiconserved cationic lipid-binding site.
Article in The Journal of biological chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Comparative genomics of nicotinic acetylcholine receptors reveals early divergence of the α6 subunit in cryptic Anopheles species.BMC genomics · 2026Article
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- The Pentameric Ligand-Gated Ion Channel Family: A New Member of the Voltage Gated Ion Channel Superfamily?International journal of molecular sciences · 2024Article
- Discovery of lipid binding sites in a ligand-gated ion channel by integrating simulations and cryo-EM.eLife · 2024Article
- Targeting ion channels with ultra-large library screening for hit discovery.Frontiers in molecular neuroscience · 2023Review
- Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation.Nature communications · 2022Article
- Structure of a cholinergic cell membrane.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- TUPÃ: Electric field analyses for molecular simulations.Journal of computational chemistry · 2022Article
- Recent Insight into Lipid Binding and Lipid Modulation of Pentameric Ligand-Gated Ion Channels.Biomolecules · 2022Review
- Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites.eLife · 2022Article
- Novel Functional Properties of Missense Mutations in the Glycine Receptor β Subunit in Startle Disease.Frontiers in molecular neuroscience · 2021Article
- Druggable Lipid Binding Sites in Pentameric Ligand-Gated Ion Channels and Transient Receptor Potential Channels.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
Pentameric ligand-gated ion channels (pLGICs) are crucial mediators of electrochemical signal transduction in various organisms from bacteria to humans. Lipids play an important role in regulating pLGIC function, yet the structural bases for specific pLGIC-lipid interactions remain poorly understood. The bacterial channel ELIC recapitulates several properties of eukaryotic pLGICs, including activation by the neurotransmitter GABA and binding and modulation by lipids, offering a simplified model system for structure-function relationship studies. In this study, functional effects of noncanonical amino acid substitution of a potential lipid-interacting residue (W206) at the top of the M1-helix, combined with detergent interactions observed in recent X-ray structures, are consistent with this region being the location of a lipid-binding site on the outward face of the ELIC transmembrane domain. Coarse-grained and atomistic molecular dynamics simulations revealed preferential binding of lipids containing a positive charge, particularly involving interactions with residue W206, consistent with cation-π binding. Polar contacts from other regions of the protein, particularly M3 residue Q264, further support lipid binding via headgroup ester linkages. Aromatic residues were identified at analogous sites in a handful of eukaryotic family members, including the human GABA
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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.