Ligands selectively tune the local and global motions of neurotensin receptor 1 (NTS1)
Neurotensin receptor
DOI:
10.1016/j.celrep.2023.112015
Publication Date:
2023-01-20T21:18:51Z
AUTHORS (11)
ABSTRACT
Nuclear magnetic resonance (NMR) studies have revealed that fast methyl sidechain dynamics can report on entropically-driven allostery. Yet, NMR applications been largely limited to the super-microsecond motional regimes of G protein-coupled receptors (GPCRs). We use 13Cε-methionine chemical shift-based global order parameters test if ligands affect a thermostabilized GPCR, neurotensin receptor 1 (NTS1). establish NTS1 solution ensemble includes substates with lifetimes several, discrete timescales. The longest-lived states reflect those captured in agonist- and inverse agonist-bound crystal structures, separated by large energy barriers. observe rapid fluctuations individual methionine residues, superimposed these long-lived states, respond collectively degree fast, correlating ligand pharmacology. This approach lends confidence interpreting spectra terms local structure dihedral angle geometry. results suggest role for sub-microsecond conformational entropy GPCR discrimination.
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