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

Cell | 2017

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.

Pubmed ID: 28753425 RIS Download

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK066202
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM109955
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008294
  • Agency: NEI NIH HHS, United States
    Id: R01 EY005216
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK071662
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM108635
  • Agency: NEI NIH HHS, United States
    Id: R01 EY011500
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM087413
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM122491

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