Disruption of a putative intersubunit electrostatic bond enhances agonist efficacy at the human α1 glycine receptor.

ABSTRACT: Partial agonists have lower efficacies than compounds considered 'full agonists', eliciting submaximal responses even at saturating concentrations. Taurine is a partial agonist at the glycine receptor (GlyR), a member of the cys-loop ligand-gated ion channel superfamily. The molecular mechanisms responsible for agonism are not fully understood but evidence suggests that efficacy at these receptors is determined by conformational changes that occur early in the process of receptor activation. We previously identified a residue located near the human α1 glycine binding site (aspartate-97; D97) that, when mutated to arginine (D97R), results in GlyR channels opening spontaneously with a high open probability, mimicking the effects of saturating glycine concentrations on wildtype GlyR. This D97

SUBMITTER: Welsh BT 

PROVIDER: S-EPMC5303145 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature