Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2.

Journal Article (Journal Article)

Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and 1H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions.

Full Text

Duke Authors

Cited Authors

  • He, Q-T; Xiao, P; Huang, S-M; Jia, Y-L; Zhu, Z-L; Lin, J-Y; Yang, F; Tao, X-N; Zhao, R-J; Gao, F-Y; Niu, X-G; Xiao, K-H; Wang, J; Jin, C; Sun, J-P; Yu, X

Published Date

  • April 22, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 2396 -

PubMed ID

  • 33888704

Pubmed Central ID

  • PMC8062632

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-021-22731-x

Language

  • eng

Conference Location

  • England