Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors.

Zhou XE, He Y, de Waal PW, Gao X, Kang Y, Van Eps N, Yin Y, Pal K, Goswami D, White TA, Barty A, Latorraca NR, Chapman HN, Hubbell WL, Dror RO, Stevens RC, Cherezov V, Gurevich VV, Griffin PR, Ernst OP, Melcher K, Xu HE
Cell. 2017 170 (3): 457-469.e13

PMID: 28753425 · PMCID: PMC5567868 · DOI:10.1016/j.cell.2017.07.002

G protein-coupled receptors (GPCRs) mediate diverse signaling in part through interaction with arrestins, whose binding promotes receptor internalization and signaling through G protein-independent pathways. High-affinity arrestin binding requires receptor phosphorylation, often at the receptor's C-terminal tail. Here, we report an X-ray free electron laser (XFEL) crystal structure of the rhodopsin-arrestin complex, in which the phosphorylated C terminus of rhodopsin forms an extended intermolecular β sheet with the N-terminal β strands of arrestin. Phosphorylation was detected at rhodopsin C-terminal tail residues T336 and S338. These two phospho-residues, together with E341, form an extensive network of electrostatic interactions with three positively charged pockets in arrestin in a mode that resembles binding of the phosphorylated vasopressin-2 receptor tail to β-arrestin-1. Based on these observations, we derived and validated a set of phosphorylation codes that serve as a common mechanism for phosphorylation-dependent recruitment of arrestins by GPCRs.

Copyright © 2017 Elsevier Inc. All rights reserved.

MeSH Terms (13)

Amino Acid Sequence Animals Arrestins Chromatography, Liquid Humans Mice Models, Molecular Phosphorylation Rats Rhodopsin Sequence Alignment Tandem Mass Spectrometry X-Rays

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