期刊
EMBO REPORTS
卷 21, 期 11, 页码 -出版社
WILEY
DOI: 10.15252/embr.202050437
关键词
G protein‐ coupled receptor; genetically encoded crosslinkers; GPCR– arrestin complexes; live cells; β ‐ arrestins
资金
- German Research Foundation (DFG) [Emmy-Noether Co822/2-1, Co822/3-1, Si867/15-2]
- Max-Buchner-Forschungsstiftung [3456]
- NIH [R35 GM122491, RO1 EY011500]
- Cornelius Vanderbilt Chair
- Projekt DEAL
beta-arrestins (beta arr1 and beta arr2) are ubiquitous regulators of G protein-coupled receptor (GPCR) signaling. Available data suggest that beta-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 beta arr1 and beta arr2 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 beta-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.
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