Ligands selectively tune the local and global motions of neurotensin receptor 1 (NTS₁).

ABSTRACT: Nuclear magnetic resonance (NMR) studies have revealed that fast methyl sidechain dynamics can report on entropically-driven allostery. Yet, NMR applications have been largely limited to the super-microsecond motional regimes of G protein-coupled receptors (GPCRs). We use ¹³C^ε-methionine chemical shift-based global order parameters to test if ligands affect the fast dynamics of a thermostabilized GPCR, neurotensin receptor 1 (NTS₁). We establish that the NTS₁ solution ensemble includes substates with lifetimes on several, discrete timescales. The longest-lived states reflect those captured in agonist- and inverse agonist-bound crystal structures, separated by large energy barriers. We observe that the rapid fluctuations of individual methionine r

SUBMITTER: Bumbak F 

PROVIDER: S-EPMC9930568 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature