Mapping spatial relationships between residues in the ligand-binding domain of the 5-HT3 receptor using a molecular ruler.

ABSTRACT: The serotonin 5-HT(3) receptor (5-HT(3)R) is a member of the Cys-loop ligand-gated ion channel family. We used a combination of site-directed mutagenesis, homology modeling, and ligand-docking simulations to analyze antagonist-receptor interactions. Mutation of E236, which is near loop C of the binding site, to aspartate prevents expression of the receptor on the cell surface, and no specific ligand binding can be detected. On the other hand, mutation to glutamine, asparagine, or alanine produces receptors that are expressed on the cell surface, but decreases receptor affinity for the competitive antagonist d-tubocurarine (dTC) 5-35-fold. The results of a double-mutant cycle analysis employing a panel of dTC analogs to identify specific points of interactions between the dTC analogs and E2

SUBMITTER: Nyce HL 

PROVIDER: S-EPMC2862198 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature