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Structure of the neurotensin receptor 1 in complex with β-arrestin 1
Open accessAbstract
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.
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“The structure of the phosphorylated human neurotensin receptor 1 with arrestin reveals a PI(4,5)P2 molecule forming a bridge between the receptor and arrestin [120,121].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [121]
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Metadata
- Authors
- Huang, W., Masureel, M., Qu, Q., Janetzko, J., Inoue, A., Kato, H. E., Robertson, M. J., Nguyen, K. C., Glenn, J. S., Skiniotis, G., & Kobilka, B. K.
- Affiliations
- Stanford Medicine (US)
- Tohoku University (JP)
- Stanford University (US)
- SLAC National Accelerator Laboratory (US)
- Corresponding author
- Skiniotis, Georgios
- Kobilka, Brian K.
- ORCID
- Venue
- Nature
- Published
- 2020-01-16
- Volume
- 579
- Issue
- 7798
- Pages
- 303-308
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7100716
- OpenAlex
- W3000145087
- Cited by
- 373
- References
- 58
- Citations by year
- 2026: 45 · 2025: 66 · 2024: 41 · 2023: 63 · 2022: 47 · 2021: 63 · 2020: 46
- FWCI
- 17.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (5u19ai109662-05)
- Japan Society for the Promotion of Science (19H03163, 17K08264)
- National Cancer Institute (P30CA124435)
- National Institute of Allergy and Infectious Diseases (U19-AI109662)
- National Institute of Neurological Disorders and Stroke (R01NS028471)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- neurotensin receptor 1, β-arrestin1, G protein-coupled receptors, receptor phosphorylation, phosphatidylinositol 4,5-bisphosphate, receptor internalization, cryo-EM structure
- MeSH terms
- beta-Arrestin 1, Humans, Models, Molecular, Phosphorylation, Receptors, Neurotensin, Cryoelectron Microscopy, Protein Structure, Quaternary, Protein Stability
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