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J Neurochem
2008 Mar 01;1046:1649-62. doi: 10.1111/j.1471-4159.2007.05090.x.
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Cross-linking of sites involved with alcohol action between transmembrane segments 1 and 3 of the glycine receptor following activation.
Lobo IA
,
Harris RA
,
Trudell JR
.
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The glycine receptor is a member of the Cys-loop, ligand-gated ion channel family and is responsible for inhibition in the CNS. We examined the orientation of amino acids I229 in transmembrane 1 (TM1) and A288 in TM3, which are both critical for alcohol and volatile anesthetic action. We mutated these two amino acids to cysteines either singly or in double mutants and expressed the receptors in Xenopus laevis oocytes. We tested whether disulfide bonds could form between A288C in TM3 paired with M227C, Y228C, I229C, or S231C in TM1. Application of cross-linking (mercuric chloride) or oxidizing (iodine) agents had no significant effect on the glycine response of wild-type receptors or the single mutants. In contrast, the glycine response of the I229C/A288C double mutant was diminished after application of either mercuric chloride or iodine only in the presence of glycine, indicating that channel gating causes I229C and A288C to fluctuate to be within 6 A apart and form a disulfide bond. Molecular modeling was used to thread the glycine receptor sequence onto a nicotinic acetylcholine receptor template, further demonstrating that I229 and A288 are near-neighbors that can cross-link and providing evidence that these residues contribute to a single binding cavity.
Akabas,
Identification of acetylcholine receptor channel-lining residues in the M1 segment of the alpha-subunit.
1995, Pubmed,
Xenbase
Akabas,
Identification of acetylcholine receptor channel-lining residues in the M1 segment of the alpha-subunit.
1995,
Pubmed
,
Xenbase
Barrantes,
Modulation of nicotinic acetylcholine receptor function through the outer and middle rings of transmembrane domains.
2003,
Pubmed
Beckstead,
Anesthetic and ethanol effects on spontaneously opening glycine receptor channels.
2002,
Pubmed
,
Xenbase
Bera,
GABA(A) receptor M2-M3 loop secondary structure and changes in accessibility during channel gating.
2002,
Pubmed
Bertaccini,
Normal-mode analysis of the glycine alpha1 receptor by three separate methods.
2007,
Pubmed
Bertaccini,
Predicting the transmembrane secondary structure of ligand-gated ion channels.
2002,
Pubmed
Bertaccini,
Homology modeling of a human glycine alpha 1 receptor reveals a plausible anesthetic binding site.
2005,
Pubmed
Bertaccini,
The common chemical motifs within anesthetic binding sites.
2007,
Pubmed
Betz,
Glycine receptors: recent insights into their structural organization and functional diversity.
2006,
Pubmed
Blanton,
Agonist-induced photoincorporation of a p-benzoylphenylalanine derivative of substance P into membrane-spanning region 2 of the Torpedo nicotinic acetylcholine receptor delta subunit.
1994,
Pubmed
Blanton,
Probing the structure of the nicotinic acetylcholine receptor ion channel with the uncharged photoactivable compound -3H-diazofluorene.
1998,
Pubmed
Blanton,
Probing the structure of the nicotinic acetylcholine receptor with the hydrophobic photoreactive probes [125I]TID-BE and [125I]TIDPC/16.
1998,
Pubmed
Blanton,
Identifying the lipid-protein interface of the Torpedo nicotinic acetylcholine receptor: secondary structure implications.
1994,
Pubmed
Bocquet,
A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family.
2007,
Pubmed
,
Xenbase
Bondarenko,
Structure of the first transmembrane domain of the neuronal acetylcholine receptor beta2 subunit.
2007,
Pubmed
Brejc,
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors.
2001,
Pubmed
Campagna-Slater,
Molecular modelling of the GABAA ion channel protein.
2007,
Pubmed
Castaldo,
A novel hyperekplexia-causing mutation in the pre-transmembrane segment 1 of the human glycine receptor alpha1 subunit reduces membrane expression and impairs gating by agonists.
2004,
Pubmed
Cheng,
Nanosecond-timescale conformational dynamics of the human alpha7 nicotinic acetylcholine receptor.
2007,
Pubmed
Cheng,
Homology modeling and molecular dynamics simulations of the alpha1 glycine receptor reveals different states of the channel.
2007,
Pubmed
Crawford,
Evidence that ethanol acts on a target in Loop 2 of the extracellular domain of alpha1 glycine receptors.
2007,
Pubmed
,
Xenbase
Dang,
Probing the role of a conserved M1 proline residue in 5-hydroxytryptamine(3) receptor gating.
2000,
Pubmed
,
Xenbase
Dellisanti,
Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution.
2007,
Pubmed
England,
Backbone mutations in transmembrane domains of a ligand-gated ion channel: implications for the mechanism of gating.
1999,
Pubmed
,
Xenbase
Ernst,
Comparative models of GABAA receptor extracellular and transmembrane domains: important insights in pharmacology and function.
2005,
Pubmed
Findlay,
Allosteric modulation in spontaneously active mutant gamma-aminobutyric acidA receptors.
2001,
Pubmed
,
Xenbase
Hemmings,
Emerging molecular mechanisms of general anesthetic action.
2005,
Pubmed
Horenstein,
Protein mobility and GABA-induced conformational changes in GABA(A) receptor pore-lining M2 segment.
2001,
Pubmed
,
Xenbase
Hughson,
Analysis of protein structure in intact cells: crosslinking in vivo between introduced cysteines in the transmembrane domain of a bacterial chemoreceptor.
1997,
Pubmed
Jenkins,
Evidence for a common binding cavity for three general anesthetics within the GABAA receptor.
2001,
Pubmed
Jung,
Functional and structural analysis of the GABAA receptor alpha 1 subunit during channel gating and alcohol modulation.
2005,
Pubmed
,
Xenbase
Jung,
Sites in TM2 and 3 are critical for alcohol-induced conformational changes in GABA receptors.
2006,
Pubmed
,
Xenbase
Keramidas,
The pre-M1 segment of the alpha1 subunit is a transduction element in the activation of the GABAA receptor.
2006,
Pubmed
Kruse,
Structure of a specific alcohol-binding site defined by the odorant binding protein LUSH from Drosophila melanogaster.
2003,
Pubmed
Lee,
Transmembrane signaling characterized in bacterial chemoreceptors by using sulfhydryl cross-linking in vivo.
1995,
Pubmed
Lee,
Identification of functionally important helical faces in transmembrane segments by scanning mutagenesis.
1995,
Pubmed
Leite,
Structure of ligand-gated ion channels: critical assessment of biochemical data supports novel topology.
2001,
Pubmed
Leite,
Coupled proteolytic and mass spectrometry studies indicate a novel topology for the glycine receptor.
2000,
Pubmed
Lester,
Cys-loop receptors: new twists and turns.
2004,
Pubmed
Lobo,
Channel gating of the glycine receptor changes accessibility to residues implicated in receptor potentiation by alcohols and anesthetics.
2004,
Pubmed
,
Xenbase
Lobo,
Sites of alcohol and volatile anesthetic action on glycine receptors.
2005,
Pubmed
Lobo,
Cross-linking of glycine receptor transmembrane segments two and three alters coupling of ligand binding with channel opening.
2004,
Pubmed
,
Xenbase
Lobo,
Accessibility to residues in transmembrane segment four of the glycine receptor.
2006,
Pubmed
Mascia,
A single amino acid determines differences in ethanol actions on strychnine-sensitive glycine receptors.
1996,
Pubmed
,
Xenbase
Mascia,
Specific binding sites for alcohols and anesthetics on ligand-gated ion channels.
2000,
Pubmed
,
Xenbase
Mihic,
Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
1997,
Pubmed
,
Xenbase
Miyazawa,
Structure and gating mechanism of the acetylcholine receptor pore.
2003,
Pubmed
Ortells,
Evolutionary history of the ligand-gated ion-channel superfamily of receptors.
1995,
Pubmed
Paas,
Pore conformations and gating mechanism of a Cys-loop receptor.
2005,
Pubmed
,
Xenbase
Purohit,
A stepwise mechanism for acetylcholine receptor channel gating.
2007,
Pubmed
Rajendra,
The glycine receptor.
1997,
Pubmed
Reeves,
Structural and electrostatic properties of the 5-HT3 receptor pore revealed by substituted cysteine accessibility mutagenesis.
2001,
Pubmed
Roberts,
Occupancy of a single anesthetic binding pocket is sufficient to enhance glycine receptor function.
2006,
Pubmed
,
Xenbase
Rosen,
Channel opening by anesthetics and GABA induces similar changes in the GABAA receptor M2 segment.
2007,
Pubmed
Sansom,
Hinges, swivels and switches: the role of prolines in signalling via transmembrane alpha-helices.
2000,
Pubmed
Sarto-Jackson,
Spontaneous cross-link of mutated alpha1 subunits during GABA(A) receptor assembly.
2007,
Pubmed
Soskine,
Crosslinking of membrane-embedded cysteines reveals contact points in the EmrE oligomer.
2002,
Pubmed
Taleb,
Expression of the human glycine receptor alpha 1 subunit in Xenopus oocytes: apparent affinities of agonists increase at high receptor density.
1994,
Pubmed
,
Xenbase
Taly,
Normal mode analysis suggests a quaternary twist model for the nicotinic receptor gating mechanism.
2005,
Pubmed
Trudell,
Comparative modeling of a GABAA alpha1 receptor using three crystal structures as templates.
2004,
Pubmed
Unwin,
Refined structure of the nicotinic acetylcholine receptor at 4A resolution.
2005,
Pubmed
Wick,
Mutations of gamma-aminobutyric acid and glycine receptors change alcohol cutoff: evidence for an alcohol receptor?
1998,
Pubmed
,
Xenbase
Winston,
Evidence that the adaptation region of the aspartate receptor is a dynamic four-helix bundle: cysteine and disulfide scanning studies.
2005,
Pubmed
Yamakura,
Anesthetics and ion channels: molecular models and sites of action.
2001,
Pubmed
Yamakura,
Amino acid volume and hydropathy of a transmembrane site determine glycine and anesthetic sensitivity of glycine receptors.
1999,
Pubmed
,
Xenbase
Yang,
Structure and function in rhodopsin. Cysteines 65 and 316 are in proximity in a rhodopsin mutant as indicated by disulfide formation and interactions between attached spin labels.
1996,
Pubmed
Yang,
Closed-state cross-linking of adjacent beta1 subunits in alpha1beta1 GABAa receptors via introduced 6' cysteines.
2007,
Pubmed
