Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mutations in the M4 domain of Torpedo californica acetylcholine receptor dramatically alter ion channel function.
Lee YH
,
Li L
,
Lasalde J
,
Rojas L
,
McNamee M
,
Ortiz-Miranda SI
,
Pappone P
.
???displayArticle.abstract???
Site-directed mutagenesis was used to mutate alpha Cys418 and beta Cys447 in the M4 domain of Torpedo californica acetylcholine receptor expressed in Xenopus laevis oocytes. The M4 region is a transmembrane domain thought to be located at the lipid-protein interface. By whole-cell voltage clamp analysis, mutation of both alpha subunits to alpha Trp418 increased maximal channel activity approximately threefold, increased the desensitization rate compared with wild-type receptor, and shifted the EC50 for acetylcholine from 32 microM to 13 microM. Patch measurements of single-channel currents revealed that the alpha Trp418 increased channel open times approximately 28-fold at 13 degrees C with no effect on channel conductance. All of our measured functional changes in the alpha Trp418 mutant are consistent with a simple kinetic model of the acetylcholine receptor in which only the channel closing rate is altered by the mutation. Our results show that changes in protein structure at the putative lipid-protein interface can dramatically affect receptor function.
Barish,
A transient calcium-dependent chloride current in the immature Xenopus oocyte.
1983, Pubmed,
Xenbase
Barish,
A transient calcium-dependent chloride current in the immature Xenopus oocyte.
1983,
Pubmed
,
Xenbase
Bertrand,
Unconventional pharmacology of a neuronal nicotinic receptor mutated in the channel domain.
1992,
Pubmed
,
Xenbase
Bhushan,
Correlation of phospholipid structure with functional effects on the nicotinic acetylcholine receptor. A modulatory role for phosphatidic acid.
1993,
Pubmed
Blanton,
Mapping the lipid-exposed regions in the Torpedo californica nicotinic acetylcholine receptor.
1992,
Pubmed
Butler,
FTIR analysis of nicotinic acetylcholine receptor secondary structure in reconstituted membranes.
1993,
Pubmed
Cachelin,
Desensitization of the acetylcholine receptor of frog end-plates measured in a Vaseline-gap voltage clamp.
1989,
Pubmed
Charnet,
An open-channel blocker interacts with adjacent turns of alpha-helices in the nicotinic acetylcholine receptor.
1990,
Pubmed
Clarke,
Labeling of functionally sensitive sulfhydryl-containing domains of acetylcholine receptor from Torpedo californica membranes.
1986,
Pubmed
Claudio,
Nucleotide and deduced amino acid sequences of Torpedo californica acetylcholine receptor gamma subunit.
1983,
Pubmed
Devillers-Thiery,
Complete mRNA coding sequence of the acetylcholine binding alpha-subunit of Torpedo marmorata acetylcholine receptor: a model for the transmembrane organization of the polypeptide chain.
1983,
Pubmed
DiPaola,
The sidedness of the COOH terminus of the acetylcholine receptor delta subunit.
1989,
Pubmed
Fong,
Stabilization of acetylcholine receptor secondary structure by cholesterol and negatively charged phospholipids in membranes.
1987,
Pubmed
Galzi,
Functional architecture of the nicotinic acetylcholine receptor: from electric organ to brain.
1991,
Pubmed
Giraudat,
Transmembrane topology of acetylcholine receptor subunits probed with photoreactive phospholipids.
1985,
Pubmed
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Heasman,
Fertilization of cultured Xenopus oocytes and use in studies of maternally inherited molecules.
1991,
Pubmed
,
Xenbase
Hucho,
The ion channel of the nicotinic acetylcholine receptor is formed by the homologous helices M II of the receptor subunits.
1986,
Pubmed
Huganir,
Properties of proteoliposomes reconstituted with acetylcholine receptor from Torpedo californica.
1982,
Pubmed
Imoto,
Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance.
1988,
Pubmed
,
Xenbase
Kao,
Identification of the alpha subunit half-cystine specifically labeled by an affinity reagent for the acetylcholine receptor binding site.
1984,
Pubmed
Kao,
Acetylcholine receptor binding site contains a disulfide cross-link between adjacent half-cystinyl residues.
1986,
Pubmed
Leonard,
Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor.
1988,
Pubmed
,
Xenbase
Lerea,
Ionotropic glutamate receptor subtypes activate c-fos transcription by distinct calcium-requiring intracellular signaling pathways.
1993,
Pubmed
Li,
Site-specific mutations of nicotinic acetylcholine receptor at the lipid-protein interface dramatically alter ion channel gating.
1992,
Pubmed
,
Xenbase
Li,
Functional role of the cysteine 451 thiol group in the M4 helix of the gamma subunit of Torpedo californica acetylcholine receptor.
1990,
Pubmed
,
Xenbase
Lingle,
Activation of skeletal muscle nicotinic acetylcholine receptors.
1992,
Pubmed
Lo,
Role of a key cysteine residue in the gating of the acetylcholine receptor.
1991,
Pubmed
,
Xenbase
Marquez,
Covalent modification of a critical sulfhydryl group in the acetylcholine receptor: cysteine-222 of the alpha-subunit.
1989,
Pubmed
Mishina,
Location of functional regions of acetylcholine receptor alpha-subunit by site-directed mutagenesis.
,
Pubmed
,
Xenbase
Mosckovitz,
Three possible disulfides in the acetylcholine receptor alpha-subunit.
1988,
Pubmed
Noda,
Structural homology of Torpedo californica acetylcholine receptor subunits.
1983,
Pubmed
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
Pradier,
Use of chemical modifications and site-directed mutagenesis to probe the functional role of thiol groups on the gamma subunit of Torpedo californica acetylcholine receptor.
1989,
Pubmed
,
Xenbase
Revah,
Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor.
1991,
Pubmed
,
Xenbase
Revah,
The noncompetitive blocker [3H]chlorpromazine labels three amino acids of the acetylcholine receptor gamma subunit: implications for the alpha-helical organization of regions MII and for the structure of the ion channel.
1990,
Pubmed
Sine,
Activation of Torpedo acetylcholine receptors expressed in mouse fibroblasts. Single channel current kinetics reveal distinct agonist binding affinities.
1990,
Pubmed
Stroud,
Nicotinic acetylcholine receptor superfamily of ligand-gated ion channels.
1990,
Pubmed
Unwin,
Nicotinic acetylcholine receptor at 9 A resolution.
1993,
Pubmed
Villarroel,
Location of a threonine residue in the alpha-subunit M2 transmembrane segment that determines the ion flow through the acetylcholine receptor channel.
1991,
Pubmed
,
Xenbase
Wallace,
Protein incorporation by isolated amphibian oocytes. 3. Optimum incubation conditions.
1973,
Pubmed
,
Xenbase
White,
Niflumic and flufenamic acids are potent reversible blockers of Ca2(+)-activated Cl- channels in Xenopus oocytes.
1990,
Pubmed
,
Xenbase
Yee,
Thiol-group modification of Torpedo californica acetylcholine receptor: subunit localization and effects on function.
1986,
Pubmed
