Neuronal nicotinic receptors: from protein structure to function
FEBS LettersPublished 28 August 2001Open access
Valérie Itier, Daniel Bertrand
Citations187
SJR quartileQ1
SJR score1.22
SNIP0.77
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TL;DR
In the light of the latest finding, the structure–function relationship of neuronal nicotinic acetylcholine receptors is reviewed and their implication in neurological diseases is reviewed.
Abstract
Neuronal nicotinic acetylcholine receptors are a prototype of ligand-gated channels that mediate transmission in the central and peripheral nervous system. Structure-function studies performed at the amino acid level are now unraveling the determinant residues either for the properties of the ligand-binding domain or the ionic pore. In this work we review, in the light of the latest finding, the structure-function relationship of these receptors and their implication in neurological diseases.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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The Journal of PhysiologyEnd‐plate channel opening and the kinetics of quinacrine (mepacrine) block.
45 Citations1980Paul R. Adams, Anne Feltz
A slow voltage dependent blockage of open end‐plate channels by quinacrine is suggested, compatible with a simple model for channel opening.
Proceedings of the National Academy of SciencesAgonist-induced closure of constitutively open γ-aminobutyric acid channels with mutated M2 domains
42 Citations1997Zhuo-Hua Pan, Dongxian Zhang +2 more
This study provides important new insights into the structure-function relationship of ligand-gated ion channels, where modification of the structure of the channel pore region not only alters the allosteric transition of the receptor protein but also reverses the polarity of agonist regulation of channel gating.
NeuropharmacologyPhosphorylation of the predicted major intracellular domains of the rat and chick neuronal nicotinic acetylcholine receptor α7 Subunit by cAMP-dependent protein kinase
41 Citations1996Stephen J. Moss, Bernard McDonald +2 more
Results demonstrate that the intracellular domain of the alpha 7 subunit is a substrate of PKA, and suggest a role for protein phosphorylation in mediating cellular regulation upon neuronal AChRs containing this subunit.
Cold Spring Harbor Symposia on Quantitative BiologyGenomic Sequences Encoding the -Subunit of Acetylcholine Receptor Are Conserved in Evolution
40 Citations1983Marc Ballivet, Patrick Nef +2 more
Biophysical JournalKinked-Helices Model of the Nicotinic Acetylcholine Receptor Ion Channel and Its Complexes with Blockers: Simulation by the Monte Carlo Minimization Method
37 Citations1998Denis B. Tikhonov, Boris S. Zhorov
It is suggested that conformational transitions in the chains Val9-Ala12 are responsible for the channel gating, whereas rotations of more stable alpha-helical parts of M2 segments may be necessary to transfer the channel in the desensitized state.
Cellular and Molecular Life SciencesAllosteric proteins after thirty years: The binding and state functions of the neuronalα7 nicotinic acetylcholine receptors
35 Citations1996Stuart J. Edelstein, J.-P. Changeux
A key statement of the 1965 Monod-Wyman-Changeux model for allosteric proteins concerns the distinction between the ligand-binding function and the relevant state function and it is suggested that hyper-responsive properties also occur with high-affinity mutants.
Journal of Molecular BiologyElectron microscopic evidence for the assembly of soluble pentameric extracellular domains of the nicotinic acetylcholine receptor
33 Citations2000M.L. Tierney, Nigel Unwin
A low-resolution, three-dimensional image of these purified complexes, composed only of ECDs, was obtained and were shown to resemble the extracellular vestibule of the native receptor, having the same pseudo-pentameric symmetry, size and shape.
Trends in Biochemical SciencesSingle channel currents in the nicotinic acetylcholine receptor: a direct demonstration of allosteric transitions
31 Citations1994Meyer B. Jackson
Unprecedented evidence from the nicotinic acetylcholine receptor is discussed that demonstrates a clear switch between conformational states with or without ligand binding, suggesting that these states pre-exis, in support of the Monod-Wyman-Changeux allosteric model.
Molecular PharmacologyAn α4β4 Nicotinic Receptor Subtype Is Present in Chick Retina: Identification, Characterization and Pharmacological Comparison with the Transfected α4β4 and α6β4 Subtypes
30 Citations2001Benedetta Barabino, Silvia Vailati +5 more
Because chick retina expresses an α6β4-containing subtype with a high affinity for the α-conotoxin MII, this work used native and transfected α4β4 and α6 β4 subtypes to investigate the relative contributions of the α and β subunits to this binding, and found that the α6 subunit determines thehigh affinity for this toxin.
Molecular PharmacologyChick Optic Lobe Contains a Developmentally Regulated α2α5β2 Nicotinic Receptor Subtype
28 Citations2000B. Balestra, Silvia Vailati +4 more
The optic lobe is the chick central nervous system region that expresses the highest level of α2-containing receptors, which form functional cationic channels when reconstituted in lipid bilayers, with pharmacological and biophysical properties different from those of the α4β2 subtype.
Protein Engineering Design and SelectionMolecular modelling of the nicotinic acetylcholine receptor transmembrane region in the open state
27 Citations1997Marcelo O. Ortells, Georgina E. Barrantes +3 more
A model of the nicotinic acetylcholine receptor transmembrane region has been constructed which may represent the channel in its open-state, and suggests some novel explanations for the results of labelling and mutation studies such as those involving ion channel blockers and residue-dependent changes in ion selectivity.
Novartis Foundation symposiumMolecular Basis of the Charge Selectivity of Nicotinic Acetylcholine Receptor and Related Ligand‐Gated Ion Channels
23 Citations2007Pierre‐Jean Corringer, Sonia Bertrand +4 more
Systematic analysis of each of these three mutations supports the notion that the conversion of ionic selectivity results from a local structural reorganization of the 234-238 loop, and a possible functional analogy with the voltage-gated ion channels and related receptors is discussed.
Annals of the New York Academy of SciencesReverse Pharmacology of the Nicotinic Acetylcholine Receptor
23 Citations1991Reid J. Leonard, Pierre Charnet +6 more
A model for the binding of QX-222 within the ion channel of the AChR that is consistent with observations is proposed, and the distance between the aromatic and quaternary amine moieties of Qx-222 corresponds almost exactly to the repeat distance of an alpha helix.
Biophysical JournalAcetylcholine receptor: channel-opening kinetics evaluated by rapid chemical kinetic and single-channel current measurements
12 Citations1987Jayant B. Udgaonkar, George P. Hess
The results confirm the assumed basic agreement between two entirely different methodologies and underlie the strategy of using the two techniques to obtain complementary information in time and ligand-concentration regions where only one or the other technique can be used.
Pflügers Archiv - European Journal of PhysiologySubunit interface selective toxins as probes of nicotinic acetylcholine receptor structure
10 Citations2000Palmer Taylor, Siobhan Malany +3 more
Identification of interactive residues through mutagenesis, when coupled with homology modeling of domains and site-directed residue modification, has revealed important elements of receptor structure.
NeuroreportNicotine facilitates noradrenaline release in the rat supraoptic nucleus
9 Citations2001Xiu Liu, Tatsushi Onaka +1 more
The results suggest that nicotine acts within the supraoptic nucleus to facilitate noradrenaline release pre-synaptically, and may contribute, in part, to vasopressin release after nicotine.
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