Structure of the vasopressin hormone–V2 receptor–β-arrestin1 ternary complex
Julien Bous, Aurélien Fouillen, Hélène Orcel, Stefano Trapani, Xiaojing Cong, Simon Fontanel, Julie Saint‐Paul, Joséphine Lai‐Kee‐Him, Serge Urbach, Nathalie Sibille, Rémy Sounier, Sébastien Granier, Bernard Mouillac, Patrick Bron
Abstract
Arrestins interact with G protein-coupled receptors (GPCRs) to stop G protein activation and to initiate key signaling pathways. Recent structural studies shed light on the molecular mechanisms involved in GPCR-arrestin coupling, but whether this process is conserved among GPCRs is poorly understood. Here, we report the cryo-electron microscopy active structure of the wild-type arginine-vasopressin V2 receptor (V2R) in complex with β-arrestin1. It reveals an atypical position of β-arrestin1 compared to previously described GPCR-arrestin assemblies, associated with an original V2R/β-arrestin1 interface involving all receptor intracellular loops. Phosphorylated sites of the V2R carboxyl terminus are clearly identified and interact extensively with the β-arrestin1 N-lobe, in agreement with structural data obtained with chimeric or synthetic systems. Overall, these findings highlight a notable structural variability among GPCR-arrestin signaling complexes.