Magnitude of a conformational change in the glycine receptor beta1-beta2 loop is correlated with agonist efficacy.

ABSTRACT: The efficacy of agonists at Cys-loop ion channel receptors is determined by the rate they isomerize receptors to a pre-open flip state. Once the flip state is reached, the shut-open reaction is similar for low and high efficacy agonists. The present study sought to identify a conformational change associated with the closed-flip transition in the alpha1-glycine receptor. We employed voltage-clamp fluorometry to compare ligand-binding domain conformational changes induced by the following agonists, listed from highest to lowest affinity and efficacy: glycine > beta-alanine > taurine. Voltage-clamp fluorometry involves labeling introduced cysteines with environmentally sensitive fluorophores and inferring structural rearrangements from ligand-induced fluorescence changes. Agonist affinity an

SUBMITTER: Pless SA 

PROVIDER: S-EPMC2785665 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature