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Comparison of taurine- and glycine-induced conformational changes in the M2-M3 domain of the glycine receptor

Han, Nian Lin; Clements, John D; Lynch, Joseph

Description

In the ionotropic glutamate receptor, the global conformational changes induced by partial agonists are smaller than those induced by full agonists. However, in the pentameric ligand-gated ion channel receptor family, the structural basis of partial agonism is not understood. This study investigated whether full and partial agonists induce different conformation changes in the glycine receptor chloride channel (GlyR). A substituted cysteine accessibility analysis demonstrated previously that...[Show more]

dc.contributor.authorHan, Nian Lin
dc.contributor.authorClements, John D
dc.contributor.authorLynch, Joseph
dc.date.accessioned2015-12-13T22:51:26Z
dc.date.available2015-12-13T22:51:26Z
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/1885/81089
dc.description.abstractIn the ionotropic glutamate receptor, the global conformational changes induced by partial agonists are smaller than those induced by full agonists. However, in the pentameric ligand-gated ion channel receptor family, the structural basis of partial agonism is not understood. This study investigated whether full and partial agonists induce different conformation changes in the glycine receptor chloride channel (GlyR). A substituted cysteine accessibility analysis demonstrated previously that glycine binding induced an increase in surface accessibility of all residues from Arg271 to Lys 276 in the M2-M3 domain of the homomeric α1 GlyR. Here we compare the surface accessibility changes induced by the full agonist, glycine, and the partial agonist, taurine. In GlyRs incorporating the A272C, S273C, L274C, or P275C mutation, the reaction rate of the cysteine-specific compound, methanethiosulfonate ethyltrimethylammonium, depended on how strongly the receptors were activated but was agonist-independent. Reaction rates could not be compared in the R271C and K276C mutant GlyRs because methanethiosulfonate ethyltrimethylammonium did not modify the extremely small currents induced by saturating taurine or equivalent low glycine concentrations. The results indicate that bound taurine and glycine molecules impose identical conformational changes to the M2-M3 domain. We therefore conclude that the higher efficacy of glycine is due to an increased ability to stabilize a common activated configuration.
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc
dc.sourceJournal of Biological Chemistry
dc.subjectKeywords: Amino acids; Ammonium compounds; Conformations; Proteins; Reaction kinetics; Conformational changes; Glutamate receptors; Ligands; Biochemistry; arginine; chloride channel; cysteine; glycine; glycine receptor; ion channel; lysine; methanethiosulfonate eth
dc.titleComparison of taurine- and glycine-induced conformational changes in the M2-M3 domain of the glycine receptor
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume279
dc.date.issued2004
local.identifier.absfor110902 - Cellular Nervous System
local.identifier.ariespublicationMigratedxPub9420
local.type.statusPublished Version
local.contributor.affiliationHan, Nian Lin, University of Queensland
local.contributor.affiliationClements, John D, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationLynch, Joseph, University of Queensland
local.bibliographicCitation.issue19
local.bibliographicCitation.startpage19559
local.bibliographicCitation.lastpage19565
local.identifier.doi10.1074/jbc.M400548200
dc.date.updated2015-12-11T10:45:23Z
local.identifier.scopusID2-s2.0-2442423159
CollectionsANU Research Publications

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