Ligand-induced conformational changes in the β1-adrenergic receptor revealed by hydrogen-deuterium exchange mass spectrometry.

ABSTRACT: G Protein Coupled Receptors (GPCRs) constitute the largest family of signalling proteins responsible for translating extracellular stimuli into intracellular functions. They play crucial roles in numerous physiological processes and are major targets for drug discovery. Dysregulation of GPCRs is implicated in various diseases, making understanding their structural dynamics critical for therapeutic development. Here, we use Hydrogen Deuterium Exchange Mass Spectrometry (HDX-MS) to explore the structural dynamics of the turkey β1-adrenergic receptor (tβ1AR) bound with nine different ligands, including agonists, partial agonists, and antagonists. We find that these ligands induce distinct dynamic patterns across the receptor, which can be grouped by compound modality. Notably, full agonist bi

SUBMITTER: Toporowska J 

PROVIDER: S-EPMC11489754 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature