Snapshot of a signalling complex

Abstract

G-protein-coupled receptors initiate signalling pathways by forming complexes with agonist molecules and G proteins. The first crystal structure of such a complex is both reassuring and provocative. See Article p.549 & Letter p.611 G-protein-coupled receptors (GPCRs) mediate the majority of a cell's responses to hormones and neurotransmitters, and to the senses of sight, olfaction and taste. This makes GPCRs potentially the most important group of drug targets in the human body. GPCRs are deeply embedded in the cell membrane, crossing it seven times, so structure determination for these complexes is particularly challenging — as recounted in a recent News Feature (see http://go.nature.com/ftqnx4 ). The eagerly-awaited X-ray crystal structure of a GPCR transmembrane signalling complex has now been determined by Brian Kobilka's group. The structure presented is of an agonist-occupied monomer of the β2 adrenergic receptor in complex with Gs, the stimulatory G protein for adenylyl cyclase. An accompanying paper reports the use of peptide amide hydrogen-deuterium exchange mass spectrometry to probe the protein dynamics of this signalling complex.