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  • Title: Conformational Basis of G Protein-Coupled Receptor Signaling Versatility.
    Author: Wingler LM, Lefkowitz RJ.
    Journal: Trends Cell Biol; 2020 Sep; 30(9):736-747. PubMed ID: 32622699.
    Abstract:
    G protein-coupled receptors (GPCRs) are privileged structural scaffolds in biology that have the versatility to regulate diverse physiological processes. Interestingly, many GPCR ligands exhibit significant 'bias' - the ability to preferentially activate subsets of the many cellular pathways downstream of these receptors. Recently, complementary information from structural and spectroscopic approaches has made significant inroads into understanding the mechanisms of these biased ligands. The consistently emerging theme is that GPCRs are highly dynamic proteins, and ligands with varying pharmacological properties differentially modulate the equilibrium among multiple conformations. Biased signaling and other recently appreciated complexities of GPCR signaling thus appear to be a natural consequence of the conformational heterogeneity of GPCRs and GPCR-transducer complexes.
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