Structure of the neurotensin receptor 1 in complex with β-arrestin 1

Arrestin proteins bind to active, phosphorylated G-protein-coupled receptors (GPCRs), thereby preventing G-protein coupling, triggering receptor internalization and affecting various downstream signalling pathways 1 , 2 . Although there is a wealth of structural information detailing the interaction...

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Veröffentlicht in:Nature (London) 2020-03, Vol.579 (7798), p.303-308
Hauptverfasser: Huang, Weijiao, Masureel, Matthieu, Qu, Qianhui, Janetzko, John, Inoue, Asuka, Kato, Hideaki E., Robertson, Michael J., Nguyen, Khanh C., Glenn, Jeffrey S., Skiniotis, Georgios, Kobilka, Brian K.
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Sprache:eng
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Zusammenfassung:Arrestin proteins bind to active, phosphorylated G-protein-coupled receptors (GPCRs), thereby preventing G-protein coupling, triggering receptor internalization and affecting various downstream signalling pathways 1 , 2 . Although there is a wealth of structural information detailing the interactions between GPCRs and G proteins, less is known about how arrestins engage GPCRs. Here we report a cryo-electron microscopy structure of full-length human neurotensin receptor 1 (NTSR1) in complex with truncated human β-arrestin 1 (βarr1(ΔCT)). We find that phosphorylation of NTSR1 is critical for the formation of a stable complex with βarr1(ΔCT), and identify phosphorylated sites in both the third intracellular loop and the C terminus that may promote this interaction. In addition, we observe a phosphatidylinositol-4,5-bisphosphate molecule forming a bridge between the membrane side of NTSR1 transmembrane segments 1 and 4 and the C-lobe of arrestin. Compared with a structure of a rhodopsin–arrestin-1 complex, in our structure arrestin is rotated by approximately 85° relative to the receptor. These findings highlight both conserved aspects and plasticity among arrestin–receptor interactions. A cryo-electron microscopy structure of the neurotensin receptor 1 in complex with β-arrestin 1 is reported.
ISSN:0028-0836
1476-4687
DOI:10.1038/s41586-020-1953-1