ArticleProceedings of the National Academy of Sciences of the United States of America2016
Identifying the elusive link between amino acid sequence and charge selectivity in pentameric ligand-gated ion channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Excitatory GABA receptors shape locomotor circuit organization in C. elegans.Scientific reports · 2026Article
- Disentangling the mechanistic role of loop-C capping in Cys-loop receptor activation.Nature communications · 2025Article
- Molecular prosthetics for CFTR designed for anion selectivity outperform amphotericin B in cultured cystic fibrosis airway epithelia.bioRxiv : the preprint server for biology · 2025Article
- Exploring the Activation Process of the Glycine Receptor.Journal of the American Chemical Society · 2024Article
- Heteromeric wild-type/mutant potassium channel subunit composition as a major determinant of channelopathy phenotype in heterozygous patients.The Journal of general physiology · 2023Article
- Lateral fenestrations in the extracellular domain of the glycine receptor contribute to the main chloride permeation pathway.Science advances · 2022Article
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- Signal transduction through Cys-loop receptors is mediated by the nonspecific bumping of closely apposed domains.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Thermodynamics and Kinetics of Ion Permeation in Wild-Type and Mutated Open Active Conformation of the Human α7 Nicotinic Receptor.Journal of chemical information and modeling · 2020Article
- A novel fast-channel myasthenia caused by mutation in β subunit of AChR reveals subunit-specific contribution of the intracellular M1-M2 linker to channel gating.Experimental neurology · 2020Article
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- Progress in nicotinic receptor structural biology.Neuropharmacology · 2020Review
- Structure of the Native Muscle-type Nicotinic Receptor and Inhibition by Snake Venom Toxins.Neuron · 2020Article
- Muscle acetylcholine receptor conversion into chloride conductance at positive potentials by a single mutation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A Crucial Role for Side-Chain Conformation in the Versatile Charge Selectivity of Cys-Loop Receptors.Biophysical journal · 2019Article
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- The dual-gate model for pentameric ligand-gated ion channels activation and desensitization.The Journal of physiology · 2018Review
- Distinct pH dependencies of NaThe Journal of biological chemistry · 2018Article
- Chasing the open-state structure of pentameric ligand-gated ion channels.The Journal of general physiology · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Among neurotransmitter-gated ion channels, the superfamily of pentameric ligand-gated ion channels (pLGICs) is unique in that its members display opposite permeant-ion charge selectivities despite sharing the same structural fold. Although much effort has been devoted to the identification of the mechanism underlying the cation-versus-anion selectivity of these channels, a careful analysis of past work reveals that discrepancies exist, that different explanations for the same phenomenon have often been put forth, and that no consensus view has yet been reached. To elucidate the molecular basis of charge selectivity for the superfamily as a whole, we performed extensive mutagenesis and electrophysiological recordings on six different cation-selective and anion-selective homologs from vertebrate, invertebrate, and bacterial origin. We present compelling evidence for the critical involvement of ionized side chains-whether pore-facing or buried-rather than backbone atoms and propose a mechanism whereby not only their charge sign but also their conformation determines charge selectivity. Insertions, deletions, and residue-to-residue mutations involving nonionizable residues in the intracellular end of the pore seem to affect charge selectivity by changing the rotamer preferences of the ionized side chains in the first turn of the M2 α-helices. We also found that, upon neutralization of the charged residues in the first turn of M2, the control of charge selectivity is handed over to the many other ionized side chains that decorate the pore. This explains the long-standing puzzle as to why the neutralization of the intracellular-mouth glutamates affects charge selectivity to markedly different extents in different cation-selective pLGICs.
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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.