ArticleNature structural & molecular biology2022
Structural mechanism of muscle nicotinic receptor desensitization and block by curare.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 79 citations in OpenAlex.
- Article
- Muscle-Specific Differences in Neuromuscular Block and Quantitative Neuromuscular Monitoring: A Narrative Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Positive allosteric modulator selective for adult muscle nicotinic acetylcholine receptor.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The PERK inhibitor GSK2606414 evokes developmental defects in zebrafish consistent with Wolcott-Rallison syndrome phenotypes.Pharmacological reports : PR · 2026Article
- Structural basis of human zinc-activated channel (ZAC) signaling and modulation.Cell discovery · 2026Article
- In Vitro and Clinical Evaluation of the Anti-Wrinkle Efficacy of Medipep-6PN, a Novel Peptide Identified by Phage Display.International journal of molecular sciences · 2026Article
- Structural insights into the progressive recovery of α7 nicotinic acetylcholine receptor from nicotine-induced desensitization.Science advances · 2025Article
- Mechanism of human α3β GlyR regulation by intracellular M3/M4 loop phosphorylation and 2,6-di-tert-butylphenol interaction.Nature communications · 2025Article
- In silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors (nAChRs) for nicotine addiction treatment.Current research in structural biology · 2025Article
- Article
- Identification of Bioactive Metabolites ofMetabolites · 2025Article
- Structural insights into the activation mechanism of the human zinc-activated channel.Nature communications · 2025Article
- Article
- Proline substitutions in the ASIC1 β11-12 linker slow desensitization.Biophysical journal · 2024Article
- Article
- A bupropion modulatory site in the Gloeobacter violaceus ligand-gated ion channel.Biophysical journal · 2024Article
- Structural bases for stoichiometry-selective calcium potentiation of a neuronal nicotinic receptor.British journal of pharmacology · 2024Article
- Proline substitutions in the ASIC1 β11-12 linker slow desensitization.bioRxiv : the preprint server for biology · 2024Article
- Influence of lipid bilayer on the structure of the muscle-type nicotinic acetylcholine receptor.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ensemble-Based Virtual Screening Led to the Discovery of Novel Lead Molecules as Potential NMBAs.Molecules (Basel, Switzerland) · 2024Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Binding of the neurotransmitter acetylcholine to its receptors on muscle fibers depolarizes the membrane and thereby triggers muscle contraction. We sought to understand at the level of three-dimensional structure how agonists and antagonists alter nicotinic acetylcholine receptor conformation. We used the muscle-type receptor from the Torpedo ray to first define the structure of the receptor in a resting, activatable state. We then determined the receptor structure bound to the agonist carbachol, which stabilizes an asymmetric, closed channel desensitized state. We find conformational changes in a peripheral membrane helix are tied to recovery from desensitization. To probe mechanisms of antagonism, we obtained receptor structures with the active component of curare, a poison arrow toxin and precursor to modern muscle relaxants. d-Tubocurarine stabilizes the receptor in a desensitized-like state in the presence and absence of agonist. These findings define the transitions between resting and desensitized states and reveal divergent means by which antagonists block channel activity of the muscle-type nicotinic receptor.
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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.