ArticleThe Journal of general physiology2008
Nicotinic receptor interloop proline anchors beta1-beta2 and Cys loops in coupling agonist binding to channel gating.
Article in The Journal of general physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Introducing a proline in the α1 M2-M3 linker relieves a molecular brake on channel activation in α1β2γ2 GABAbioRxiv : the preprint server for biology · 2026Article
- Introducing a proline in the α1 M2-M3 linker relieves a molecular brake on channel activation in α1β2γ2 GABAA receptors.PloS one · 2026Article
- Disentangling the mechanistic role of loop-C capping in Cys-loop receptor activation.Nature communications · 2025Article
- A release of local subunit conformational heterogeneity underlies gating in a muscle nicotinic acetylcholine receptor.Nature communications · 2024Article
- Recent Insight into Lipid Binding and Lipid Modulation of Pentameric Ligand-Gated Ion Channels.Biomolecules · 2022Review
- Progress in nicotinic receptor structural biology.Neuropharmacology · 2020Review
- Mutagenesis computer experiments in pentameric ligand-gated ion channels: the role of simulation tools with different resolution.Interface focus · 2019Review
- Cryo-EM structure of 5-HTNature communications · 2018Article
- Mutational Analysis at Intersubunit Interfaces of an Anionic Glutamate Receptor Reveals a Key Interaction Important for Channel Gating by Ivermectin.Frontiers in molecular neuroscience · 2017Article
- A mechanism for acetylcholine receptor gating based on structure, coupling, phi, and flip.The Journal of general physiology · 2017Article
- X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors.Nature · 2014Article
- Allosteric regulation of pentameric ligand-gated ion channels: an emerging mechanistic perspective.Channels (Austin, Tex.) · 2014Review
- A gating mechanism of pentameric ligand-gated ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2013Review
- The energy and work of a ligand-gated ion channel.Journal of molecular biology · 2013Review
- Loop C and the mechanism of acetylcholine receptor-channel gating.The Journal of general physiology · 2013Article
- Size matters in activation/inhibition of ligand-gated ion channels.Trends in pharmacological sciences · 2012Review
- Myasthenic syndrome AChRα C-loop mutant disrupts initiation of channel gating.The Journal of clinical investigation · 2012Article
- Contributions of conserved residues at the gating interface of glycine receptors.The Journal of biological chemistry · 2011Article
- Design and control of acetylcholine receptor conformational change.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Mapping heat exchange in an allosteric protein.Biophysical journal · 2011Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Nicotinic acetylcholine receptors (AChRs) mediate rapid excitatory synaptic transmission throughout the peripheral and central nervous systems. They transduce binding of nerve-released ACh into opening of an intrinsic channel, yet the structural basis underlying transduction is not fully understood. Previous studies revealed a principal transduction pathway in which alphaArg 209 of the pre-M1 domain and alphaGlu 45 of the beta1-beta2 loop functionally link the two regions, positioning alphaVal 46 of the beta1-beta2 loop in a cavity formed by alphaPro 272 through alphaSer 269 of the M2-M3 loop. Here we investigate contributions of residues within and proximal to this pathway using single-channel kinetic analysis, site-directed mutagenesis, and thermodynamic mutant cycle analysis. We find that in contributing to channel gating, alphaVal 46 and alphaVal 132 of the signature Cys loop couple energetically to alphaPro 272. Furthermore, these residues are optimized in both their size and hydrophobicity to mediate rapid and efficient channel gating, suggesting naturally occurring substitutions at these positions enable a diverse range of gating rate constants among the Cys-loop receptor superfamily. The overall results indicate that alphaPro 272 functionally couples to flanking Val residues extending from the beta1-beta2 and Cys loops within the ACh binding to channel opening transduction pathway.
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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.