ArticleNature2011
Tunable pKa values and the basis of opposite charge selectivities in nicotinic-type receptors.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- PIP2-driven cytoplasmic domain motions are coupled to Kir2 channel gating.The Journal of general physiology · 2025Article
- Ion transport in muscle acetylcholine receptor maintained by conserved salt bridges between the pore and lipid membrane.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Subunit gating resulting from individual protonation events in Kir2 channels.Nature communications · 2023Article
- Subunit gating resulting from individual protonation events in Kir2 channels.Research square · 2023Article
- Unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptor.eLife · 2021Article
- Mechanisms of activation and desensitization of full-length glycine receptor in lipid nanodiscs.Nature communications · 2020Article
- The dual-gate model for pentameric ligand-gated ion channels activation and desensitization.The Journal of physiology · 2018Review
- Inhibitory mechanism of peptides with a repeating hydrophobic and hydrophilic residue pattern on interleukin-10.Human vaccines & immunotherapeutics · 2017Article
- Identifying the elusive link between amino acid sequence and charge selectivity in pentameric ligand-gated ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Syndromic deafness mutations at Asn 14 differentially alter the open stability of Cx26 hemichannels.The Journal of general physiology · 2016Article
- Membrane environment modulates the pKa values of transmembrane helices.The journal of physical chemistry. B · 2015Article
- Approaching the 5-HT₃ receptor heterogeneity by computational studies of the transmembrane and intracellular domains.Journal of computer-aided molecular design · 2013Article
- Novel missense mutations in the glycine receptor β subunit gene (GLRB) in startle disease.Neurobiology of disease · 2013Article
- NMR resolved multiple anesthetic binding sites in the TM domains of the α4β2 nAChR.Biochimica et biophysica acta · 2013Article
- Buried lysine, but not arginine, titrates and alters transmembrane helix tilt.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Emerging approaches to probing ion channel structure and function.Neuroscience bulletin · 2012Review
- Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path and locates a "bottleneck" in the pore.Biochemistry · 2012Article
- Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin.Frontiers in molecular neuroscience · 2012Article
- Molecular dissection of Cl--selective Cys-loop receptor points to components that are dispensable or essential for channel activity.The Journal of biological chemistry · 2011Article
- Charge substitution for a deep-pore residue reveals structural dynamics during BK channel gating.The Journal of general physiology · 2011Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Among ion channels, only the nicotinic-receptor superfamily has evolved to generate both cation- and anion-selective members. Although other, structurally unrelated, neurotransmitter-gated cation channels exist, no other type of neurotransmitter-gated anion channel, and thus no other source of fast synaptic inhibitory signals, has been described so far. In addition to the seemingly straightforward electrostatic effect of the presence (in the cation-selective members) or absence (in the anion-selective ones) of a ring of pore-facing carboxylates, mutational studies have identified other features of the amino-acid sequence near the intracellular end of the pore-lining transmembrane segments (M2) that are also required to achieve the high charge selectivity shown by native channels. However, the mechanism underlying this more subtle effect has remained elusive and a subject of speculation. Here we show, using single-channel electrophysiological recordings to estimate the protonation state of native ionizable side chains, that anion-selective-type sequences favour whereas cation-selective-type sequences prevent the protonation of the conserved, buried basic residues at the intracellular entrance of the pore (the M2 0' position). We conclude that the previously unrecognized tunable charge state of the 0' ring of buried basic side chains is an essential feature of these channels' versatile charge-selectivity filter.
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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.