A 1,350-base-pair-long cDNA clone, named p alpha-2, was isolated by hybridization to the previously characterized clone p alpha-1 and found to be specific for the alpha-subunit of the Torpedo marmorata acetylcholine receptor. The nucleotide sequences of both cDNA inserts were analyzed and the sequence of the complete coding region and part of the 5' and 3' untranslated regions of the alpha-chain mRNA was determined. The complete amino acid sequence of the alpha-chain precursor is presented and used to develop a model for the transmembrane organization of the polypeptide.
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http://dx.doi.org/10.1073/pnas.80.7.2067 | DOI Listing |
Nat Commun
February 2024
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
Synaptic receptors respond to neurotransmitters by opening an ion channel across the post-synaptic membrane to elicit a cellular response. Here we use recent Torpedo acetylcholine receptor structures and functional measurements to delineate a key feature underlying allosteric communication between the agonist-binding extracellular and channel-gating transmembrane domains. Extensive mutagenesis at this inter-domain interface re-affirms a critical energetically coupled role for the principal α subunit β1-β2 and M2-M3 loops, with agonist binding re-positioning a key β1-β2 glutamate/valine to facilitate the outward motions of a conserved M2-M3 proline to open the channel gate.
View Article and Find Full Text PDFNat Commun
August 2022
Laboratory of Structural Neurobiology, Department of Cellular and Molecular Medicine, Faculty of Medicine, KU Leuven, 3000, Leuven, Belgium.
Bites by elapid snakes (e.g. cobras) can result in life-threatening paralysis caused by venom neurotoxins blocking neuromuscular nicotinic acetylcholine receptors.
View Article and Find Full Text PDFNeuron
April 2022
Université Grenoble Alpes, CNRS, CEA, IBS, F-38000 Grenoble, France. Electronic address:
Fast synaptic communication requires receptors that respond to the presence of neurotransmitter by opening an ion channel across the post-synaptic membrane. The muscle-type nicotinic acetylcholine receptor from the electric fish, Torpedo, is the prototypic ligand-gated ion channel, yet the structural changes underlying channel activation remain undefined. Here we use cryo-EM to solve apo and agonist-bound structures of the Torpedo nicotinic receptor embedded in a lipid nanodisc.
View Article and Find Full Text PDFData Brief
October 2020
Department of the Biology, University of Puerto Rico, Río Piedras Campus, San Juan, Puerto Rico.
For a long time, traditional purification and extraction methods for the native nicotinic acetylcholine receptor in lipid-like detergent complex (nAChR-DC) have compromised its purity, functionality and X-ray structural studies possibility. The dataset presented in this article provide a characterization of the nAChR-DC purified using a sequential purification processes developed in our laboratory [1]. This purification takes in consideration all of the physicochemical and functional requirements stablished by several researchers for the past three decades for the nAChR.
View Article and Find Full Text PDFJ Biol Chem
August 2020
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada
The activity of the muscle-type nicotinic acetylcholine receptor (nAChR) is highly sensitive to lipids, but the underlying mechanisms remain poorly understood. The nAChR transmembrane α-helix, M4, is positioned at the perimeter of each subunit in direct contact with lipids and likely plays a central role in lipid sensing. To gain insight into the mechanisms underlying nAChR lipid sensing, we used homology modeling, coevolutionary analyses, site-directed mutagenesis, and electrophysiology to examine the role of the α-subunit M4 (αM4) in the function of the adult muscle nAChR.
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