ArticleThe Journal of biological chemistry2011
Two neuronal nicotinic acetylcholine receptors, alpha4beta4 and alpha7, show differential agonist binding modes.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Targeted Mutations Activate Allosteric Modulation of α5-Containing Nicotinic Acetylcholine Receptors.ACS chemical neuroscience · 2026Article
- Conopeptides as Modulators of Pain and Inflammation in Chemotherapy-Induced Peripheral Neuropathy by Targeting α7 and α9 Nicotinic Acetylcholine Receptors.Neurotoxicity research · 2026Review
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Controlling Doxorubicin Release from a Peptide Hydrogel through Fine-Tuning of Drug-Peptide Fiber Interactions.Biomacromolecules · 2022Article
- Article
- A potential interaction between the SARS-CoV-2 spike protein and nicotinic acetylcholine receptors.Biophysical journal · 2021Article
- Nicotinic receptor pharmacology in silico: Insights and challenges.Neuropharmacology · 2020Review
- An Investigation of Three-Finger Toxin-nAChR Interactions through Rosetta Protein Docking.Toxins · 2020Article
- Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors.bioRxiv : the preprint server for biology · 2020Article
- A Methyl Scan of the Pyrrolidinium Ring of Nicotine Reveals Significant Differences in Its Interactions withMolecular pharmacology · 2020Article
- In Silico Modeling of the α7 Nicotinic Acetylcholine Receptor: New Pharmacological Challenges Associated with Multiple Modes of Signaling.Mini reviews in medicinal chemistry · 2020Review
- A human-specific, truncated α7 nicotinic receptor subunit assembles with full-length α7 and forms functional receptors with different stoichiometries.The Journal of biological chemistry · 2018Article
- Competitive docking model for prediction of the human nicotinic acetylcholine receptor α7 binding of tobacco constituents.Oncotarget · 2018Article
- Probing for and Quantifying Agonist Hydrogen Bonds in α6β2 Nicotinic Acetylcholine Receptors.Biochemistry · 2017Article
- The binding orientation of epibatidine at α7 nACh receptors.Neuropharmacology · 2017Article
- Crystal structure of a human neuronal nAChR extracellular domain in pentameric assembly: Ligand-bound α2 homopentamer.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- An Unaltered Orthosteric Site and a Network of Long-Range Allosteric Interactions for PNU-120596 in α7 Nicotinic Acetylcholine Receptors.Chemistry & biology · 2015Article
- Varenicline Interactions at the 5-HT3 Receptor Ligand Binding Site are Revealed by 5-HTBP.ACS chemical neuroscience · 2015Article
- Incorporation of Non-Canonical Amino Acids.Advances in experimental medicine and biology · 2015Review
- Functional evaluation of key interactions evident in the structure of the eukaryotic Cys-loop receptor GluCl.ACS chemical biology · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Nicotinic acetylcholine receptors (nAChRs) are pentameric, neurotransmitter-gated ion channels responsible for rapid excitatory neurotransmission in the central and peripheral nervous systems, resulting in skeletal muscle tone and various cognitive effects in the brain. These complex proteins are activated by the endogenous neurotransmitter ACh as well as by nicotine and structurally related agonists. Activation and modulation of nAChRs has been implicated in the pathology of multiple neurological disorders, and as such, these proteins are established therapeutic targets. Here we use unnatural amino acid mutagenesis to examine the ligand binding mechanisms of two homologous neuronal nAChRs: the α4β4 and α7 receptors. Despite sequence identity among the residues that form the core of the agonist-binding site, we find that the α4β4 and α7 nAChRs employ different agonist-receptor binding interactions in this region. The α4β4 receptor utilizes a strong cation-π interaction to a conserved tryptophan (TrpB) of the receptor for both ACh and nicotine, and nicotine participates in a strong hydrogen bond with a backbone carbonyl contributed by TrpB. Interestingly, we find that the α7 receptor also employs a cation-π interaction for ligand recognition, but the site has moved to a different aromatic amino acid of the agonist-binding site depending on the agonist. ACh participates in a cation-π interaction with TyrA, whereas epibatidine participates in a cation-π interaction with TyrC2.
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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.