Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation.

ABSTRACT: G-protein-coupled receptors (GPCRs) modulate many physiological processes by transducing a variety of extracellular cues into intracellular responses. Ligand binding to an extracellular orthosteric pocket propagates conformational change to the receptor cytosolic region to promote binding and activation of downstream signalling effectors such as G proteins and β-arrestins. It is well known that different agonists can share the same binding pocket but evoke unique receptor conformations leading to a wide range of downstream responses (‘efficacy’). Furthermore, increasing biophysical evidence, primarily using the β2-adrenergic receptor (β2AR) as a model system, supports the existence of multiple active and inactive conformational states. However, how agonists with varying efficacy modulate t

SUBMITTER: Staus DP 

PROVIDER: S-EPMC4961583 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature