Elucidation of a dynamic interplay between a beta-2 adrenergic receptor, its agonist, and stimulatory G protein.

ABSTRACT: G protein-coupled receptors (GPCRs) represent the largest group of membrane receptors for transmembrane signal transduction. Ligand-induced activation of GPCRs triggers G protein activation followed by various signaling cascades. Understanding the structural and energetic determinants of ligand binding to GPCRs and GPCRs to G proteins is crucial to the design of pharmacological treatments targeting specific conformations of these proteins to precisely control their signaling properties. In this study, we focused on interactions of a prototypical GPCR, beta-2 adrenergic receptor (β₂AR), with its endogenous agonist, norepinephrine (NE), and the stimulatory G protein (G_s). Using molecular dynamics (MD) simulations, we demonstrated the stabilization of cationic NE, NE(+),

SUBMITTER: Han Y 

PROVIDER: S-EPMC10013855 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature