ArticleNature2014
X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.
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Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 249 citations in OpenAlex.
- A Pharmacological Perspective on Plant-derived Bioactive Molecules for Epilepsy.Neurochemical research · 2021Pooled it
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- Lethal effects of ivermectin structures on malaria vectors and in silico analysis of interactions with their glutamate-gated chloride ion channels.Scientific reports · 2026Article
- Polypharmacology of anthelmintics at host and parasite ion channels.PLoS pathogens · 2026Article
- Asymmetric gating of a homopentameric ion channel GLIC revealed by cryo-EM.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Fluorescence-detection size-exclusion chromatography specifically detects autoantibodies targeting the ganglionic acetylcholine receptor in patients with autoimmune autonomic ganglionopathy.Journal of neuroimmunology · 2024Article
- Streptomyces avermitilis MICNEMA2022: a new biorational strain for producing abamectin as an integrated nematode management agent.BMC microbiology · 2024Article
- Discovery of lipid binding sites in a ligand-gated ion channel by integrating simulations and cryo-EM.eLife · 2024Article
- The modes of action of ion-channel-targeting neurotoxic insecticides: lessons from structural biology.Nature structural & molecular biology · 2023Review
- Structural insights into opposing actions of neurosteroids on GABANature communications · 2023Article
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- A new family of glutamate-gated chloride channels in parasitic sea louse Caligus rogercresseyi: A subunit refractory to activation by ivermectin is dominant in heteromeric assemblies.PLoS pathogens · 2023Article
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- Cryo-EM structure supports a role of AQP7 as a junction protein.Nature communications · 2023Article
- Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation.Nature communications · 2022Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Speculation on How RIC-3 and Other Chaperones Facilitate α7 Nicotinic Receptor Folding and Assembly.Molecules (Basel, Switzerland) · 2022Review
- Molecular encoding and synaptic decoding of context during salt chemotaxis in C. elegans.Nature communications · 2022Article
- Database of glutamate-gated chloride (GluCl) subunits across 125 nematode species: patterns of gene accretion and sequence diversification.G3 (Bethesda, Md.) · 2022Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Cys-loop receptors are neurotransmitter-gated ion channels that are essential mediators of fast chemical neurotransmission and are associated with a large number of neurological diseases and disorders, as well as parasitic infections. Members of this ion channel superfamily mediate excitatory or inhibitory neurotransmission depending on their ligand and ion selectivity. Structural information for Cys-loop receptors comes from several sources including electron microscopic studies of the nicotinic acetylcholine receptor, high-resolution X-ray structures of extracellular domains and X-ray structures of bacterial orthologues. In 2011 our group published structures of the Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in complex with the allosteric partial agonist ivermectin, which provided insights into the structure of a possibly open state of a eukaryotic Cys-loop receptor, the basis for anion selectivity and channel block, and the mechanism by which ivermectin and related molecules stabilize the open state and potentiate neurotransmitter binding. However, there remain unanswered questions about the mechanism of channel opening and closing, the location and nature of the shut ion channel gate, the transitions between the closed/resting, open/activated and closed/desensitized states, and the mechanism by which conformational changes are coupled between the extracellular, orthosteric agonist binding domain and the transmembrane, ion channel domain. Here we present two conformationally distinct structures of C. elegans GluCl in the absence of ivermectin. Structural comparisons reveal a quaternary activation mechanism arising from rigid-body movements between the extracellular and transmembrane domains and a mechanism for modulation of the receptor by phospholipids.
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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.