Allosteric effect of nanobody binding on ligand-specific active states of the β2-adrenergic receptor

Abstract

G-protein coupled receptors (GPCRs) transduce binding of extracellular ligands into intracellular signals. They are implicated in a variety of physiological processes and represent targets for many approved drugs. To fulfill their biological role, GPCRs cycle between different activation states, ranging from fully inactive to fully active. Binding of agonists shifts the overall GPCR population towards more active states. However, it is well established that the fully activated state can only be stabilized by the binding of intracellular binding partners such as G-proteins.