|Title||Distinct conformations of GPCR-β-arrestin complexes mediate desensitization, signaling, and endocytosis.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Cahill, T. J., A. R. B. Thomsen, J. T. Tarrasch, B. Plouffe, A. H. Nguyen, F. Yang, L-Y. Huang, A. W. Kahsai, D. L. Bassoni, B. J. Gavino, J. E. Lamerdin, S. Triest, A. K. Shukla, B. Berger, J. Little, A. Antar, A. Blanc, C-X. Qu, X. Chen, K. Kawakami, A. Inoue, J. Aoki, J. Steyaert, J-P. Sun, M. Bouvier, G. Skiniotis, and R. J. Lefkowitz|
|Journal||Proc Natl Acad Sci U S A|
|Date Published||2017 Mar 07|
β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize G protein signaling, to initiate signaling on their own, and to mediate receptor endocytosis. Prior structural studies have revealed two unique conformations of GPCR-βarr complexes: the "tail" conformation, with βarr primarily coupled to the phosphorylated GPCR C-terminal tail, and the "core" conformation, where, in addition to the phosphorylated C-terminal tail, βarr is further engaged with the receptor transmembrane core. However, the relationship of these distinct conformations to the various functions of βarrs is unknown. Here, we created a mutant form of βarr lacking the "finger-loop" region, which is unable to form the core conformation but retains the ability to form the tail conformation. We find that the tail conformation preserves the ability to mediate receptor internalization and βarr signaling but not desensitization of G protein signaling. Thus, the two GPCR-βarr conformations can carry out distinct functions.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|
|PubMed Central ID||PMC5347553|
|Grant List||R01 DK090165 / DK / NIDDK NIH HHS / United States |
F30 HL129803 / HL / NHLBI NIH HHS / United States
T32 HL007101 / HL / NHLBI NIH HHS / United States
R01 HL016037 / HL / NHLBI NIH HHS / United States
T32 GM007171 / GM / NIGMS NIH HHS / United States
R01 GM069905 / GM / NIGMS NIH HHS / United States
Distinct conformations of GPCR-β-arrestin complexes mediate desensitization, signaling, and endocytosis.