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 pro-vide limited information about dynamics and conformational transitions that play pivotal roles in mediating signaling diversity through the multifaceted interactions between ligands, receptors, and transducers. Devel-oping 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 chal-lenges and limitations of19F NMR for studying GPCR dynamics are also discussed, along with experimental strategies that will drive this field forward.

Automated summary

Advances in X-ray crystallography and cryoelectron microscopy have provided insights into GPCR activation processes, but these static structures have limitations in revealing dynamics and conformational transitions. Developing NMR techniques can lead to a more comprehensive understanding of signaling processes, but challenges remain.