ArticleProceedings of the National Academy of Sciences of the United States of America2009
Unliganded gating of acetylcholine receptor channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
70 citing papers in PubMed, 96 citations in OpenAlex.
- Article
- State-dependent energetics of GABABiophysical journal · 2024Article
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- Dynamics of receptor activation by agonists.Biophysical journal · 2024Review
- Cryo-EM structures of prokaryotic ligand-gated ion channel GLIC provide insights into gating in a lipid environment.Nature communications · 2024Article
- Mechanism of hydrophobic gating in the acetylcholine receptor channel pore.The Journal of general physiology · 2024Article
- Article
- Benzodiazepine Modulation of GABABiomolecules · 2022Review
- The surprising difficulty of "simple" equilibrium binding measurements on ligand-gated ion channels.The Journal of general physiology · 2022Article
- Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously.eLife · 2022Article
- Probing function in ligand-gated ion channels without measuring ion transport.The Journal of general physiology · 2022Article
- Mapping Electromechanical Coupling Pathways in Voltage-Gated Ion Channels: Challenges and the Way Forward.Journal of molecular biology · 2021Review
- Agonist efficiency from concentration-response curves: Structural implications and applications.Biophysical journal · 2021Article
- A critical residue in the αeLife · 2021Article
- Pathways for nicotinic receptor desensitization.The Journal of general physiology · 2020Article
- The dual-gate model for pentameric ligand-gated ion channels activation and desensitization.The Journal of physiology · 2018Review
- Decrypting the Heat Activation Mechanism of TRPV1 Channel by Molecular Dynamics Simulation.Biophysical journal · 2018Article
- Cyclic activation of endplate acetylcholine receptors.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Monod-Wyman-Changeux Analysis of Ligand-Gated Ion Channel Mutants.The journal of physical chemistry. B · 2017Article
- Molecular recognition at cholinergic synapses: acetylcholine versus choline.The Journal of physiology · 2017Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
We estimated the unliganded opening and closing rate constants of neuromuscular acetylcholine receptor-channels (AChRs) having mutations that increased the gating equilibrium constant. For some mutant combinations, spontaneous openings occurred in clusters. For 25 different constructs, the unliganded gating equilibrium constant (E(0)) was correlated with the product of the predicted fold-increase in the diliganded gating equilibrium constant caused by each mutation alone. We estimate that (i) E(0) for mouse, wild-type alpha(2)beta delta epsilon AChRs is approximately 1.15 x 10(-7); (ii) unliganded AChRs open for approximately 80 micros, once every approximately 15 min; (iii) the affinity for ACh of the O(pen) conformation is approximately 10 nM, or approximately 15,600 times greater than for the C(losed) conformation; (iv) the ACh-monoliganded gating equilibrium constant is approximately 1.7 x 10(-3); (v) the C-->O isomerization reduces substantially ACh dissociation, but only slightly increases association; and (vi) ACh provides only approximately 0.9 k(B)T more binding energy per site than carbamylcholine but approximately 3.1 k(B)T more than choline, mainly because of a low O conformation affinity. Most mutations of binding site residue alphaW149 increase E(0). We estimate that the mutation alphaW149F reduces the ACh affinity of C only by 13-fold, but of O by 190-fold. Rate-equilibrium free-energy relationships for different regions of the protein show similar slopes (Phi values) for un- vs. diliganded gating, which suggests that the conformational pathway of the gating structural change is fundamentally the same with and without agonists. Agonist binding is a perturbation that (like most mutations) changes the energy, but not the mechanism, of the gating conformational change.
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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.