Distinct conformations of GPCR–β-arrestin complexes mediate desensitization, signaling, and endocytosis

• DOI: 10.1073/pnas.1701529114
• Publication Date: 2017-02-22T01:40:29Z
• Authors: Thomas J. Cahill; Alex R. B. Thomsen; Jeffrey T. Tarrasch; Bianca Plouffe; Anthony H. Nguyen; Fan Yang; Li-Yin Huang; Alem W. Kahsai; Daniel L. Bassoni; Bryant J. Gavino; Jane E. Lamerdin; Sarah Triest; Arun K. Shukla; Benjamin Berger; John Little; Albert Antar; Adi Blanc; Chang-Xiu Qu; Xin Chen; Kouki Kawakami; Asuka Inoue; Junken Aoki; Jan Steyaert; Jin-Peng Sun; Michel Bouvier; Georgios Skiniotis; Robert J. Lefkowitz
• Keywords: Internalization; Arrestin

β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize protein signaling, initiate signaling on their own, and mediate receptor endocytosis. Prior structural studies have revealed two unique conformations of GPCR-βarr complexes: the "tail" conformation, βarr primarily coupled phosphorylated GPCR C-terminal tail, "core" where, in addition is further engaged transmembrane core. However, relationship these distinct various functions βarrs unknown. Here, we created a mutant form lacking "finger-loop" region, which unable core conformation but retains ability tail conformation. We find that preserves internalization not desensitization signaling. Thus, can carry out functions.