Structural and dynamic insights into the activation of the μ-opioid receptor by an allosteric modulator.

ABSTRACT: G-protein-coupled receptors (GPCRs) play pivotal roles in various physiological processes. These receptors are activated to different extents by diverse orthosteric ligands and allosteric modulators. However, the mechanisms underlying these variations in signaling activity by allosteric modulators remain largely elusive. Here, we determine the three-dimensional structure of the μ-opioid receptor (MOR), a class A GPCR, in complex with the G_i protein and an allosteric modulator, BMS-986122, using cryogenic electron microscopy. Our results reveal that BMS-986122 binding induces changes in the map densities corresponding to R167^3.50 and Y254^5.58, key residues in the structural motifs conserved among class A GPCRs. Nuclear magnetic resonance analyses of MOR in t

SUBMITTER: Kaneko S 

PROVIDER: S-EPMC11091225 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature