ArticleProceedings of the National Academy of Sciences of the United States of America2006
Implications of the quaternary twist allosteric model for the physiology and pathology of nicotinic acetylcholine receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 94 citations in OpenAlex.
- Insights into mechanisms of MALT1 allostery from NMR and AlphaFold dynamic analyses.Communications biology · 2024Article
- Unravelling nicotinic receptor and ligand features underlying neonicotinoid knockdown actions on the malaria vector mosquitoOpen biology · 2024Article
- Allosteric Cholesterol Site in Glycine Receptors Characterized through Molecular Simulations.The journal of physical chemistry. B · 2024Article
- A single molecular distance predicts agonist binding energy in nicotinic receptors.The Journal of general physiology · 2019Article
- The neural γJournal of molecular modeling · 2018Article
- The nicotinic acetylcholine receptor: a typical 'allosteric machine'.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Loops D, E and G in the Drosophila Dα1 subunit contribute to high neonicotinoid sensitivity of Dα1-chicken β2 nicotinic acetylcholine receptor.British journal of pharmacology · 2018Article
- The dual-gate model for pentameric ligand-gated ion channels activation and desensitization.The Journal of physiology · 2018Review
- A combined coarse-grained and all-atom simulation of TRPV1 channel gating and heat activation.The Journal of general physiology · 2015Article
- Normal mode dynamics of voltage-gated K(+) channels: gating principle, opening mechanism, and inhibition.Journal of computational neuroscience · 2015Article
- Article
- International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands.Pharmacological reviews · 2014Article
- Conotoxins targeting nicotinic acetylcholine receptors: an overview.Marine drugs · 2014Review
- Pentameric Ligand-gated Ion Channels : Insights from Computation.Molecular simulation · 2014Article
- Allosteric regulation of pentameric ligand-gated ion channels: an emerging mechanistic perspective.Channels (Austin, Tex.) · 2014Review
- Long distance effect on ligand-gated ion channels extracellular domain may affect interactions with the intracellular machinery.Communicative & integrative biology · 2014Article
- Conformational changes in acetylcholine binding protein investigated by temperature accelerated molecular dynamics.PloS one · 2014Article
- 50 years of allosteric interactions: the twists and turns of the models.Nature reviews. Molecular cell biology · 2013Review
- Effects of neuronal nicotinic acetylcholine receptor allosteric modulators in animal behavior studies.Biochemical pharmacology · 2013Review
- A gating mechanism of pentameric ligand-gated ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2013Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nicotinic acetylcholine receptors (nAChR) are pentameric ligand-gated ion channels composed of subunits that consist of an extracellular domain that carries the ligand-binding site and a distinct ion-pore domain. Signal transduction results from the allosteric coupling between the two domains: the distance from the binding site to the gate of the pore domain is 50 A. Normal mode analysis with a C(alpha) Gaussian network of a new structural model of the neuronal alpha7 nAChR showed that the lowest mode involves a global quaternary twist motion that opens the ion pore. A molecular probe analysis, in which the network is modified at each individual amino acid residue, demonstrated that the major effect is to change the frequency, but not the form, of the twist mode. The largest effects were observed for the ligand-binding site and the Cys-loop. Most (24/27) of spontaneous mutations known to cause congenital myasthenia and autosomal dominant nocturnal frontal lobe epilepsy are located either at the interface between subunits or, within a given subunit, at the interface between rigid blocks. These interfaces are modified significantly by the twist mode. The present analysis, thus, supports the quaternary twist model of the nAChR allosteric transition and provides a qualitative interpretation of the effect of the mutations responsible for several receptor pathologies.
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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.