The influence of lipids and biological membranes on the conformational equilibria of GPCRs: Insights from NMR spectroscopy.

G protein-coupled receptors (GPCRs) function within cellular membranes, complex and dynamic environments. Rather than serving as a passive background, lipid membranes actively influence GPCR drug responses and signaling. Studies utilizing nuclear magnetic resonance (NMR) spectroscopy have revealed key insights into receptor-lipid interactions, enabled by the compatibility of NMR experiments with many different membrane systems and physiological temperature, conditions more closely reflecting the native cellular environment. NMR data have revealed new mechanistic insights that explain how specific lipids regulate GPCR activation, how bulk membrane properties influence receptor dynamics, and how different membrane mimetics affect GPCR behavior. These findings establish a framework for bridging in vitro structural studies with in vivo biological and pharmacological data.