Identification of a new ligand binding domain in the alpha1 subunit of the inhibitory glycine receptor.

摘要: Four discontinuous extracellular sequence domains have been proposed to form the ligand binding sites of ligand-gated ion channel receptor superfamily. In this study, we investigated role 12 contiguous residues inhibitory glycine that define loop A domain; Using techniques site-directed mutagenesis and patch-clamp electrophysiology, four were shown impaired binding. Three mutants, I93A, A101H, N102A, resulted in significant (17-44-fold) increases agonist EC50 values as compared with wild-type receptor, whereas Hill coefficients, I-max values, antagonist affinity remained largely unaffected. Consideration efficacy indicates these are involved rather than activation. fourth mutant, W94A, failed give rise any glycine-activated currents, although cell-surface expression was observed, suggesting residue may also be These data provide most extensive characterization domain available date two new locations, Ile(93) Asn(102), contributing four-loop model