Location-biased β-arrestin conformations direct GPCR signaling.

β-arrestins are multifunctional intracellular proteins that regulate the desensitization, internalization and signaling of over 800 different G protein-coupled receptors (GPCRs) and interact with a diverse array of cellular partners. Beyond the plasma membrane, GPCRs can initiate unique signaling cascades from various subcellular locations, a phenomenon known as "location bias". Here, we investigate how β-arrestins direct location-biased signaling of the angiotensin II type I receptor (AT1R).