Emerging structural insights into biased GPCR signaling

Abstract

The discovery of biased signaling at G protein-coupled receptors (GPCRs), the largest class of cell surface receptors and primary drug targets for numerous human diseases, has redefined the classical concepts of receptor pharmacology. It not only highlights the depth of signaling diversity within the GPCR system, but also offers possibilities for novel and more-effective therapeutics. Here, we highlight the recent biophysical and structural advances in our understanding of ligand-receptor interactions and conformational changes in the receptors, which provide novel mechanistic insights into biased GPCR signaling. We also underline key aspects of GPCR-biased signaling that remain to be investigated in greater detail to develop a complete molecular understanding of this process and overall GPCR signaling.

Keywords: G protein-coupled receptors (GPCRs); biased agonism; biased signaling; β-arrestin; β2 adrenergic receptor’.