Characterization of a glycine receptor domain that controls the binding and gating mechanisms of the β‐amino acid agonist, taurine

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Abstract
The β‐amino acid, taurine, is a full agonist of the human glycine receptor α1 subunit when recombinantly expressed in a mammalian (HEK293) cell line, but a partial agonist of the same receptor when expressed inXenopusoocytes. Several residues in the Ala101–Thr112 domain have previously been identified as determinants of β‐amino acid binding and gating mechanisms inXenopusoocyte‐expressed receptors. The present study used the substituted cysteine accessibility method to investigate the role of this domain in controlling taurine‐specific binding and gating mechanisms of glycine receptors recombinantly expressed in mammalian cells. Asn102 and Glu103 are identified as taurine and glycine binding sites, whereas Ala101 is eliminated as a possible binding site. The N102C mutation also abolished the antagonistic actions of taurine, indicating that this site does not discriminate between the putative agonist‐ and antagonist‐bound conformations of β‐amino acids. The effects of mutations from Lys104–Thr112 indicate that the mechanism by which this domain controls β‐amino acid‐specific binding and gating processes differs substantially depending on whether the receptor is expressed in mammalian cells orXenopusoocytes. Thr112 is the only domain element in mammalian cell‐expressed GlyRs which was demonstrated to discriminate between glycine and taurine.