Comparison of taurine- and glycine-induced conformational changes in the M2-M3 domain of the glycine receptor
Date
2004
Authors
Han, Nian Lin
Clements, John D
Lynch, Joseph
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Biochemistry and Molecular Biology Inc
Abstract
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 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.
Description
Keywords
Keywords: 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
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Source
Journal of Biological Chemistry
Type
Journal article