Structural biology of G protein-coupled receptors: new opportunities from XFELs and cryoEM

G protein-coupled receptors mediate cell signaling and regulate the majority of sensory and physiological processes in the human body. Recent breakthroughs in cryo-electron microscopy and X-ray free electron lasers have accelerated structural studies of difficult-to-crystallize receptors and their signaling complexes, and have opened up new opportunities in understanding conformational dynamics and visualizing the process of receptor activation with unprecedented spatial and temporal resolution. Here, we summarize major milestones and challenges associated with the application of these techniques and outline future directions in their development with a focus on membrane protein structural biology.