Structural insight into allosteric modulation of protease-activated receptor 2
April 26, 2017|Nature|Structural insight into allosteric modulation of protease-activated receptor 2
Protease-activated receptors (PARs) are a family of G-protein-coupled receptors (GPCRs) that are irreversibly activated by proteolytic cleavage of the N terminus, which unmasks a tethered peptide ligand that binds and activates the transmembrane receptor domain, eliciting a cellular cascade in response to inflammatory signals and other stimuli. PARs are implicated in a wide range of diseases, such as cancer and inflammation1, 2, 3. PARs have been the subject of major pharmaceutical research efforts3 but the discovery of small-molecule antagonists that effectively bind them has proved challenging.