Exploring GPCR‐arrestin interfaces with genetically encoded crosslinkers

Abstract: β‐arrestins (βarr1 and βarr2) are ubiquitous regulators of G protein‐coupled receptor (GPCR) signaling. Available data suggest that β‐arrestins dock to different receptors in different ways. However, the structural characterization of GPCR‐arrestin complexes is challenging and alternative approaches to study GPCR‐arrestin complexes are needed. Here, starting from the finger loop as a major site for the interaction of arrestins with GPCRs, we genetically incorporate non‐canonical amino acids for photo‐ and chemical crosslinking into βarr1 and βarr2 and explore binding topologies to GPCRs forming either stable or transient complexes with arrestins: the vasopressin receptor 2 (rhodopsin‐like), the corticotropin‐releasing factor receptor 1, and the parathyroid hormone receptor 1 (both secretin‐like). We show that each receptor leaves a unique footprint on arrestins, whereas the two β‐arrestins yield quite similar crosslinking patterns. Furthermore, we show that the method allows defining the orientation of arrestin with respect to the GPCR. Finally, we provide direct evidence for the formation of arrestin oligomers in the cell.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Exploring GPCR‐arrestin interfaces with genetically encoded crosslinkers ; volume:21 ; number:11 ; year:2020 ; extent:11 ; EMBO reports / European Molecular Biology Organization ; 21, Heft 11 (2020) (gesamt 11)

Contributors, Places and Time

• Creator: Böttke, Thore ; Ernicke, Stefan ; Serfling, Robert ; Ihling, Christian ; Burda, Edyta ; Gurevich, Vsevolod V. ; Sinz, Andrea ; Coin, Irene

Further information

• DOI: 10.15252/embr.202050437
• URN: urn:nbn:de:101:1-2022062911045082112390
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:20 AM CEST