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Publication Abstract from PubMed

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 beta-arrestin1. It reveals an atypical position of beta-arrestin1 compared to previously described GPCR-arrestin assemblies, associated with an original V2R/beta-arrestin1 interface involving all receptor intracellular loops. Phosphorylated sites of the V2R carboxyl terminus are clearly identified and interact extensively with the beta-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.

Structure of the vasopressin hormone-V2 receptor-beta-arrestin1 ternary complex.,Bous J, Fouillen A, Orcel H, Trapani S, Cong X, Fontanel S, Saint-Paul J, Lai-Kee-Him J, Urbach S, Sibille N, Sounier R, Granier S, Mouillac B, Bron P Sci Adv. 2022 Sep 2;8(35):eabo7761. doi: 10.1126/sciadv.abo7761. Epub 2022 Sep 2. PMID:36054364^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.