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Proc Natl Acad Sci U S A
2001 Jan 30;983:1241-8. doi: 10.1073/pnas.98.3.1241.
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Acetylcholine receptor channel structure in the resting, open, and desensitized states probed with the substituted-cysteine-accessibility method.
Wilson G
,
Karlin A
.
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The nicotinic acetylcholine (ACh) receptors cycle among classes of nonconducting resting states, conducting open states, and nonconducting desensitized states. We previously probed the structure of the mouse-muscle ACh receptor channel in the resting state obtained in the absence of agonist and in the open states obtained after brief exposure to ACh. We now have probed the structure in the stable desensitized state obtained after many minutes of exposure to ACh. Muscle-type receptor has the subunit composition alpha(2)betagammadelta. Each subunit has four membrane-spanning segments, M1-M4. The channel lumen in the membrane domain is lined largely by M2 and to a lesser extent by M1 from each of the subunits. We determined the rates of reaction of a small, sulfhydryl-specific, charged reagent, 2-aminoethyl methanethiosulfonate with cysteines substituted for residues in alphaM2 and the alphaM1-M2 loop in the desensitized state and compared these rates to rates previously obtained in the resting and open states. The reaction rates of the substituted cysteines are different in the three functional states of the receptor, indicating significant structural differences. By comparing the rates of reaction of extracellularly and intracellularly added 2-aminoethyl methanethiosulfonate, we previously located the closed gate in the resting state between alphaG240 and alphaT244, in the predicted M1-M2 loop at the intracellular end of M2. Now, we have located the closed gate in the stable desensitized state between alphaG240 and alphaL251. The gate in the desensitized state includes the resting state gate and an extension further into M2.
Akabas,
Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the alpha subunit.
1994, Pubmed,
Xenbase
Akabas,
Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the alpha subunit.
1994,
Pubmed
,
Xenbase
Akabas,
Identification of acetylcholine receptor channel-lining residues in the M1 segment of the alpha-subunit.
1995,
Pubmed
,
Xenbase
Akabas,
Acetylcholine receptor channel structure probed in cysteine-substitution mutants.
1992,
Pubmed
,
Xenbase
Auerbach,
Desensitization of mouse nicotinic acetylcholine receptor channels. A two-gate mechanism.
1998,
Pubmed
Bertrand,
Properties of neuronal nicotinic acetylcholine receptor mutants from humans suffering from autosomal dominant nocturnal frontal lobe epilepsy.
1998,
Pubmed
,
Xenbase
Bertrand,
Unconventional pharmacology of a neuronal nicotinic receptor mutated in the channel domain.
1992,
Pubmed
,
Xenbase
Blanton,
Probing the structure of the nicotinic acetylcholine receptor with the hydrophobic photoreactive probes [125I]TID-BE and [125I]TIDPC/16.
1998,
Pubmed
Boyd,
Desensitization of membrane-bound Torpedo acetylcholine receptor by amine noncompetitive antagonists and aliphatic alcohols: studies of [3H]acetylcholine binding and 22Na+ ion fluxes.
1984,
Pubmed
Buckingham,
Functional characterization of a mutated chicken alpha7 nicotinic acetylcholine receptor subunit with a leucine residue inserted in transmembrane domain 2.
1998,
Pubmed
,
Xenbase
Cachelin,
Desensitization of the acetylcholine receptor of frog end-plates measured in a Vaseline-gap voltage clamp.
1989,
Pubmed
Campos-Caro,
Role of the putative transmembrane segment M3 in gating of neuronal nicotinic receptors.
1997,
Pubmed
,
Xenbase
Charnet,
An open-channel blocker interacts with adjacent turns of alpha-helices in the nicotinic acetylcholine receptor.
1990,
Pubmed
Chesnut,
Two-component desensitization at the neuromuscular junction of the frog.
1983,
Pubmed
Corringer,
Critical elements determining diversity in agonist binding and desensitization of neuronal nicotinic acetylcholine receptors.
1998,
Pubmed
,
Xenbase
Cox,
Time-resolved photolabeling by quinacrine azide of a noncompetitive inhibitor site of the nicotinic acetylcholine receptor in a transient, agonist-induced state.
1985,
Pubmed
Damle,
Effects of agonists and antagonists on the reactivity of the binding site disulfide in acetylcholine receptor from Torpedo californica.
1980,
Pubmed
Devillers-Thiéry,
Stratified organization of the nicotinic acetylcholine receptor channel.
1992,
Pubmed
,
Xenbase
Dilger,
Desensitization of acetylcholine receptors in BC3H-1 cells.
1992,
Pubmed
DiPaola,
Mapping the alpha-subunit site photolabeled by the noncompetitive inhibitor [3H]quinacrine azide in the active state of the nicotinic acetylcholine receptor.
1990,
Pubmed
Feltz,
Desensitization at the frog neuromuscular junction: a biphasic process.
1982,
Pubmed
Filatov,
The role of conserved leucines in the M2 domain of the acetylcholine receptor in channel gating.
1995,
Pubmed
,
Xenbase
Franke,
A molecular scheme for the reaction between acetylcholine and nicotinic channels.
1993,
Pubmed
Galzi,
Allosteric transitions of the acetylcholine receptor probed at the amino acid level with a photolabile cholinergic ligand.
1991,
Pubmed
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Heidmann,
Characterization of the transient agonist-triggered state of the acetylcholine receptor rapidly labeled by the noncompetitive blocker [3H]chlorpromazine: additional evidence for the open channel conformation.
1986,
Pubmed
Heidmann,
Rapid kinetics of agonist binding and permeability response analyzed in parallel on acetylcholine receptor rich membranes from Torpedo marmorata.
1983,
Pubmed
Heidmann,
Interaction of a fluorescent agonist with the membrane-bound acetylcholine receptor from Torpedo marmorata in the millisecond time range: resolution of an "intermediate" conformational transition and evidence for positive cooperative effects.
1980,
Pubmed
Hess,
Determination of the chemical mechanism of neurotransmitter receptor-mediated reactions by rapid chemical kinetic techniques.
1993,
Pubmed
Horn,
Asymmetry of the acetylcholine channel revealed by quaternary anesthetics.
1980,
Pubmed
Javitch,
A cysteine residue in the third membrane-spanning segment of the human D2 dopamine receptor is exposed in the binding-site crevice.
1994,
Pubmed
Javitch,
Mapping the binding-site crevice of the dopamine D2 receptor by the substituted-cysteine accessibility method.
1995,
Pubmed
Jones,
The impact of receptor desensitization on fast synaptic transmission.
1996,
Pubmed
Kao,
Acetylcholine receptor binding site contains a disulfide cross-link between adjacent half-cystinyl residues.
1986,
Pubmed
Karlin,
Substituted-cysteine accessibility method.
1998,
Pubmed
Karlin,
Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins.
1995,
Pubmed
KATZ,
A study of the desensitization produced by acetylcholine at the motor end-plate.
1957,
Pubmed
Kuryatov,
Mutation causing autosomal dominant nocturnal frontal lobe epilepsy alters Ca2+ permeability, conductance, and gating of human alpha4beta2 nicotinic acetylcholine receptors.
1997,
Pubmed
,
Xenbase
Labarca,
Channel gating governed symmetrically by conserved leucine residues in the M2 domain of nicotinic receptors.
1995,
Pubmed
,
Xenbase
Lee,
Mutations in the M4 domain of Torpedo californica acetylcholine receptor dramatically alter ion channel function.
1994,
Pubmed
,
Xenbase
Lester,
Acetylcholine receptor desensitization induced by nicotine in rat medial habenula neurons.
1995,
Pubmed
Magleby,
A study of desensitization of acetylcholine receptors using nerve-released transmitter in the frog.
1981,
Pubmed
McCarthy,
Effects of lipids and detergents on the conformation of the nicotinic acetylcholine receptor from Torpedo californica.
1992,
Pubmed
Middleton,
Photoaffinity labeling the torpedo nicotinic acetylcholine receptor with [(3)H]tetracaine, a nondesensitizing noncompetitive antagonist.
1999,
Pubmed
Milone,
Slow-channel myasthenic syndrome caused by enhanced activation, desensitization, and agonist binding affinity attributable to mutation in the M2 domain of the acetylcholine receptor alpha subunit.
1997,
Pubmed
Neher,
Local anaesthetics transiently block currents through single acetylcholine-receptor channels.
1978,
Pubmed
Neher,
The charge carried by single-channel currents of rat cultured muscle cells in the presence of local anaesthetics.
1983,
Pubmed
Neubig,
Conformations of Torpedo acetylcholine receptor associated with ion transport and desensitization.
1982,
Pubmed
Neubig,
Permeability control by cholinergic receptors in Torpedo postsynaptic membranes: agonist dose-response relations measured at second and millisecond times.
1980,
Pubmed
Ochoa,
Desensitization of the nicotinic acetylcholine receptor: molecular mechanisms and effect of modulators.
1989,
Pubmed
Osaka,
Distinctions in agonist and antagonist specificity conferred by anionic residues of the nicotinic acetylcholine receptor.
1998,
Pubmed
Pascual,
Delimiting the binding site for quaternary ammonium lidocaine derivatives in the acetylcholine receptor channel.
1998,
Pubmed
,
Xenbase
Pascual,
State-dependent accessibility and electrostatic potential in the channel of the acetylcholine receptor. Inferences from rates of reaction of thiosulfonates with substituted cysteines in the M2 segment of the alpha subunit.
1998,
Pubmed
,
Xenbase
Pedersen,
Structure of the noncompetitive antagonist-binding site of the Torpedo nicotinic acetylcholine receptor. [3H]meproadifen mustard reacts selectively with alpha-subunit Glu-262.
1992,
Pubmed
Revah,
Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor.
1991,
Pubmed
,
Xenbase
Reynolds,
Molecular weight in detergent solution of acetylcholine receptor from Torpedo californica.
1978,
Pubmed
Roberts,
Reactivity of small thiolate anions and cysteine-25 in papain toward methyl methanethiosulfonate.
1986,
Pubmed
Sakmann,
Single acetylcholine-activated channels show burst-kinetics in presence of desensitizing concentrations of agonist.
1980,
Pubmed
Sine,
Mutation of the acetylcholine receptor alpha subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity.
1995,
Pubmed
Stauffer,
Electrostatic potential of the acetylcholine binding sites in the nicotinic receptor probed by reactions of binding-site cysteines with charged methanethiosulfonates.
1994,
Pubmed
Swope,
Phosphorylation of the nicotinic acetylcholine receptor by protein tyrosine kinases.
1995,
Pubmed
Unwin,
Arrangement of the acetylcholine receptor subunits in the resting and desensitized states, determined by cryoelectron microscopy of crystallized Torpedo postsynaptic membranes.
1988,
Pubmed
Unwin,
Projection structure of the nicotinic acetylcholine receptor: distinct conformations of the alpha subunits.
1996,
Pubmed
Unwin,
Acetylcholine receptor channel imaged in the open state.
1995,
Pubmed
Wang,
Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating.
1999,
Pubmed
Weiland,
An amino acid exchange in the second transmembrane segment of a neuronal nicotinic receptor causes partial epilepsy by altering its desensitization kinetics.
1996,
Pubmed
,
Xenbase
White,
Agonist-induced changes in the structure of the acetylcholine receptor M2 regions revealed by photoincorporation of an uncharged nicotinic noncompetitive antagonist.
1992,
Pubmed
Wilson,
The intrinsic electrostatic potential and the intermediate ring of charge in the acetylcholine receptor channel.
2000,
Pubmed
,
Xenbase
Wilson,
The location of the gate in the acetylcholine receptor channel.
1998,
Pubmed
Zhang,
Contribution of the beta subunit M2 segment to the ion-conducting pathway of the acetylcholine receptor.
1998,
Pubmed
,
Xenbase
Zhang,
Identification of acetylcholine receptor channel-lining residues in the M1 segment of the beta-subunit.
1997,
Pubmed
,
Xenbase
