#Allosteric activator full

In recent years, much hope came from the discovery of allosteric modulators targeting GPCRs with a few already on the market 3. They constitute the main targets in drug development programs for many therapeutic applications 2. G protein-coupled receptors (GPCR) constitute the largest family of integral membrane receptors encoded in the human genome and are involved in various physiological processes 1. Our results provide important insights on the role of allosteric modulators in mGlu activation, by stabilizing the active state of a receptor that is otherwise rapidly oscillating between active and inactive states.

#Allosteric activator full

Full activation is only observed in the presence of a PAM or the G i protein. We show that glutamate only partially stabilizes the extracellular domains in the active state. Here, we explore the effect of a PAM on the structural dynamics of mGlu2 in optimized detergent micelles using single molecule FRET at submillisecond timescales. Metabotropic glutamate receptors (mGlu) are G protein-coupled receptors that represent promising targets for brain diseases, and for which PAMs acting in the transmembrane domain have been developed. How such compounds can allosterically influence agonist action remains unclear. Much hope in drug development comes from the discovery of positive allosteric modulators (PAM) that display target subtype selectivity and act by increasing agonist potency and efficacy.