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Publication Abstract from PubMed

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 delineating the interactions between GPCRs and G proteins, less is known about how arrestins engage GPCRs. Here we report a cryo-EM structure of full-length human neurotensin receptor 1 (NTSR1) in complex with truncated human beta-arrestin 1 (betaarr1(DeltaCT)). We found that phosphorylation of NTSR1 was critical for obtaining a stable complex with betaarr1(DeltaCT), and identified phosphorylated sites in both the third intracellular loop and the C terminus that may promote this interaction. In addition, we observed a phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) molecule forming a bridge between the membrane side of NTSR1 transmembrane segments 1 and 4 and the C-lobe of arrestin. Compared to a structure of rhodopsin-arrestin-1, our structure displays an approximately 85 degrees rotation of arrestin relative to the receptor. These findings highlight both conserved aspects but also the plasticity of arrestin-receptor interactions.

Structure of the neurotensin receptor 1 in complex with beta-arrestin 1.,Huang W, Masureel M, Qianhui Q, Janetzko J, Inoue A, Kato HE, Robertson MJ, Nguyen KC, Glenn JS, Skiniotis G, Kobilka BK Nature. 2020 Jan 16. pii: 10.1038/s41586-020-1953-1. doi:, 10.1038/s41586-020-1953-1. PMID:31945771^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.