Restructuring G-Protein-Coupled Receptor Activation

G-protein-coupled receptors serve as key signal transduction conduits, linking extracellular inputs with diverse cellular responses. These receptors eluded structural characterization for decades following their identification. A landmark structure of rhodopsin provided a basis for structure-function studies and homology modeling, but advances in receptor biology suffered from a lack of receptor-specific structural insights. The recent explosion in GPCR structures confirms some features predicted by rhodopsin-based models, and more importantly, it reveals unexpected ligand-binding modes and critical aspects of the receptor activation process. The new structures also promise to foster studies testing emerging models for GPCR function such as receptor dimerization and ligand-biased signaling.