Single-molecule view of slow and sequential conformational transitions of A2A adenosine receptor

G protein-coupled receptors (GPCRs) are expressed in all human tissues and have an important role in human physiology. The human genome encodes for more than 800 GPCRs that represent major targets for FDA-approved drugs. GPCRs are allosteric machines that bind many types of ligands on their extracellular surface and undergo conformational changes of the seven-transmembrane domain (7TM) that activate signal transduction pathways inside the cell. These ligand-dependent conformational dynamics and activation of receptors during signaling remain elusive.