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

Weijiao Huang, Matthieu Masureel, Qianhui Qu, John Janetzko, Asuka Inoue, Hideaki E. Kato, Michael J. Robertson, Khanh C. Nguyen, Jeffrey S. Glenn, Georgios Skiniotis, Brian K. Kobilka

Research output: Contribution to journalArticlepeer-review

206 Citations (Scopus)


Arrestin proteins bind to active, phosphorylated G-protein-coupled receptors (GPCRs), thereby preventing G-protein coupling, triggering receptor internalization and affecting various downstream signalling pathways1,2. 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.

Original languageEnglish
Pages (from-to)303-308
Number of pages6
Issue number7798
Publication statusPublished - 2020 Mar 12


Dive into the research topics of 'Structure of the neurotensin receptor 1 in complex with β-arrestin 1'. Together they form a unique fingerprint.

Cite this