Biased Ligands Differentially Shape the Conformation of the Extracellular Loop Region in 5-HT_2B Receptors.

ABSTRACT: G protein-coupled receptors are linked to various intracellular transducers, each pathway associated with different physiological effects. Biased ligands, capable of activating one pathway over another, are gaining attention for their therapeutic potential, as they could selectively activate beneficial pathways whilst avoiding those responsible for adverse effects. We performed molecular dynamics simulations with known β-arrestin-biased ligands like lysergic acid diethylamide and ergotamine in complex with the 5-HT_2B receptor and discovered that the extent of ligand bias is directly connected with the degree of closure of the extracellular loop region. Given a loose allosteric coupling of extracellular and intracellular receptor regions, we delineate a concept for biased signali

SUBMITTER: Denzinger K 

PROVIDER: S-EPMC7767279 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature