Ligand efficacy modulates conformational dynamics of the µ-opioid receptor.

ABSTRACT: The µ-opioid receptor (µOR) is an important target for pain management¹ and molecular understanding of drug action on µOR will facilitate the development of better therapeutics. Here we show, using double electron-electron resonance and single-molecule fluorescence resonance energy transfer, how ligand-specific conformational changes of µOR translate into a broad range of intrinsic efficacies at the transducer level. We identify several conformations of the cytoplasmic face of the receptor that interconvert on different timescales, including a pre-activated conformation that is capable of G-protein binding, and a fully activated conformation that markedly reduces GDP affinity within the ternary complex. Interaction of β-arrestin-1 with the μOR core binding site appears less spec

SUBMITTER: Zhao J 

PROVIDER: S-EPMC11078757 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature