Journal
NATURE
Volume 579, Issue 7798, Pages 303-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-020-1953-1
Keywords
-
Categories
Funding
- National Institutes of Health [R01NS028471, 1U19AI109662, P30 CA124435]
- Mathers Foundation
- American Heart Association postdoctoral fellowship [17POST33410958]
- Damon Runyon Cancer Research Foundation [DRG-2318-18]
- Japan Agency for Medical Research and Development (AMED [18gm5910013, 18gm0010004]
- KAKENHI from the Japan Society for the Promotion of Science (JSPS) [17K08264]
- KAKENHI from JSPS [19H03163]
- Naito Foundation
- Kurata Grants from The Hitachi Global Foundation
- Tokyo Biochemical Research Foundation
- Grants-in-Aid for Scientific Research [19H03163] Funding Source: KAKEN
Ask authors/readers for more resources
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 beta-arrestin 1 (beta arr1(Delta CT)). We find that phosphorylation of NTSR1 is critical for the formation of a stable complex with beta arr1(Delta CT), 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 degrees 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 beta-arrestin 1 is reported.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available