Agonist-selective recruitment of engineered protein probes and of GRK2 by opioid receptors in living cells.

ABSTRACT: G protein-coupled receptors (GPCRs) signal through allostery, and it is increasingly clear that chemically distinct agonists can produce different receptor-based effects. It has been proposed that agonists selectively promote receptors to recruit one cellular interacting partner over another, introducing allosteric 'bias' into the signaling system. However, the underlying hypothesis - that different agonists drive GPCRs to engage different cytoplasmic proteins in living cells - remains untested due to the complexity of readouts through which receptor-proximal interactions are typically inferred. We describe a cell-based assay to overcome this challenge, based on GPCR-interacting biosensors that are disconnected from endogenous transduction mechanisms. Focusing on opioid receptors, we direc

SUBMITTER: Stoeber M 

PROVIDER: S-EPMC7041944 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature