Structural and functional characterization of G protein-coupled receptors with deep mutational scanning.

ABSTRACT: The >800 human G protein-coupled receptors (GPCRs) are responsible for transducing diverse chemical stimuli to alter cell state- and are the largest class of drug targets. Their myriad structural conformations and various modes of signaling make it challenging to understand their structure and function. Here, we developed a platform to characterize large libraries of GPCR variants in human cell lines with a barcoded transcriptional reporter of G protein signal transduction. We tested 7800 of 7828 possible single amino acid substitutions to the beta-2 adrenergic receptor (β₂AR) at four concentrations of the agonist isoproterenol. We identified residues specifically important for β₂AR signaling, mutations in the human population that are potentially loss of function, an

SUBMITTER: Jones EM 

PROVIDER: S-EPMC7707821 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature