Structuring the GPCR Story Through the Lens of NMR.

G-protein-coupled receptors (GPCRs) are the largest and most heterogeneous group of cell membrane receptors dictating various physiological processes. GPCRs are the pivotal points for orchestrating almost every cellular response, making them the most sought-after drug targets. Although the GPCRs have extensively been studied, there are still many aspects that are yet to be understood. The GPCR structures have been characterised using various biophysical techniques like x-ray crystallography, cryo-EM and nuclear magnetic resonance (NMR) techniques. While the conventional techniques enabled a gross understanding of the GPCR structures, ligand interaction and conformational dynamics, the recent developments in NMR methods have unlocked new possibilities to better understand receptor bias, ligand-selectivity determination and ligand-binding characterisation in live cells. In this review, we have attempted to highlight how different NMR approaches can be utilised to add more details to the story of GPCRs.