¹⁹F NMR: A promising tool for dynamic conformational studies of G protein-coupled receptors

Advances in X-ray crystallography and cryoelectron microscopy enabled unprecedented insights into the activation processes of G protein-coupled receptors (GPCRs). However, these static receptor structures provide limited information about dynamics and conformational transitions that play pivotal roles in mediating signaling diversity through the multifaceted interactions between ligands, receptors, and transducers. Developing NMR approaches to probe the dynamics of conformational transitions will push the frontier of receptor science toward a more comprehensive understanding of these signaling processes. Although much progress has been made during the last decades, it remains challenging to delineate receptor conformational states and interrogate the functions of the individual states at a quantitative level. Here we cover the progress of ¹⁹F NMR applications in GPCR conformational and dynamic studies during the past 20 years. Current challenges and limitations of ¹⁹F NMR for studying GPCR dynamics are also discussed, along with experimental strategies that will drive this field forward.