ArticleNature2005
Probing ion-channel pores one proton at a time.
Article in Nature, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
89 citing papers in PubMed, 159 citations in OpenAlex.
- Disentangling the mechanistic role of loop-C capping in Cys-loop receptor activation.Nature communications · 2025Article
- Key role of the TM2-TM3 loop in calcium potentiation of the α9α10 nicotinic acetylcholine receptor.Cellular and molecular life sciences : CMLS · 2024Article
- Mechanism of hydrophobic gating in the acetylcholine receptor channel pore.The Journal of general physiology · 2024Article
- Subunit gating resulting from individual protonation events in Kir2 channels.Nature communications · 2023Article
- Endogenous pannexin1 channels form functional intercellular cell-cell channels with characteristic voltage-dependent properties.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A photoreactive analog of allopregnanolone enables identification of steroid-binding sites in a nicotinic acetylcholine receptor.The Journal of biological chemistry · 2019Article
- A Crucial Role for Side-Chain Conformation in the Versatile Charge Selectivity of Cys-Loop Receptors.Biophysical journal · 2019Article
- A cation-π interaction in a transmembrane helix of vacuolar ATPase retains the proton-transporting arginine in a hydrophobic environment.The Journal of biological chemistry · 2018Article
- Selective ion permeation involves complexation with carboxylates and lysine in a model human sodium channel.PLoS computational biology · 2018Article
- Chasing the open-state structure of pentameric ligand-gated ion channels.The Journal of general physiology · 2017Article
- Article
- Unique Contributions of an Arginine Side Chain to Ligand Recognition in a Glutamate-gated Chloride Channel.The Journal of biological chemistry · 2017Article
- Engineering differential charge selectivity from a single structural template.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- 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
- Ionization Properties of Histidine Residues in the Lipid Bilayer Membrane Environment.The Journal of biological chemistry · 2016Article
- Side chain flexibility and the pore dimensions in the GABAA receptor.Journal of computer-aided molecular design · 2016Article
- Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels.Nature structural & molecular biology · 2016Review
- The atypical cation-conduction and gating properties of ELIC underscore the marked functional versatility of the pentameric ligand-gated ion-channel fold.The Journal of general physiology · 2015Article
- Arginine: Its pKa value revisited.Protein science : a publication of the Protein Society · 2015Article
- Correlating structural and energetic changes in glycine receptor activation.The Journal of biological chemistry · 2015Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Although membrane proteins often rely on ionizable residues for structure and function, their ionization states under physiological conditions largely elude experimental estimation. To gain insight into the effect of the local microenvironment on the proton affinity of ionizable residues, we have engineered individual lysines, histidines and arginines along the alpha-helical lining of the transmembrane pore of the nicotinic acetylcholine receptor. We can detect individual proton binding-unbinding reactions electrophysiologically at the level of a single proton on a single side chain as brief blocking-unblocking events of the passing cation current. Kinetic analysis of these fluctuations yields the position-dependent rates of proton transfer, from which the corresponding pK(a) values and shifts in pK(a) can be calculated. Here we present a self-consistent, residue-by-residue description of the microenvironment around the pore-lining transmembrane alpha-helices (M2) in the open-channel conformation, in terms of the excess free energy that is required to keep the engineered basic side chains protonated relative to bulk water. A comparison with closed-channel data leads us to propose that the rotation of M2, which is frequently invoked as a hallmark of the gating mechanism of Cys-loop receptors, is minimal, if any.
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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.