Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1.

ABSTRACT: The conformational ensembles of G protein-coupled receptors (GPCRs) include inactive and active states. Spectroscopy techniques, including NMR, show that agonists, antagonists and other ligands shift the ensemble toward specific states depending on the pharmacological efficacy of the ligand. How receptors recognize ligands and the kinetic mechanism underlying this population shift is poorly understood. Here, we investigate the kinetic mechanism of neurotensin recognition by neurotensin receptor 1 (NTS₁) using ¹⁹F-NMR, hydrogen-deuterium exchange mass spectrometry and stopped-flow fluorescence spectroscopy. Our results indicate slow-exchanging conformational heterogeneity on the extracellular surface of ligand-bound NTS₁. Numerical analysis of the kinetic da

SUBMITTER: Asadollahi K 

PROVIDER: S-EPMC10710507 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature