6UP7

neurotensin receptor and arrestin2 complex

Summary for 6UP7

• Entry DOI: 10.2210/pdb6up7/pdb
• EMDB information: 20836
• Descriptor: ARG-ARG-PRO-TYR-ILE-LEU, Beta-arrestin-1, Neurotensin receptor type 1, ... (5 entities in total)
• Functional Keywords: gpcr signaling, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 78773.03

Authors

Qu, Q.H.,Huang, W.,Masureel, M.,Janetzko, J.,Kobilka, B.K.,Skiniotis, G. (deposition date: 2019-10-16, release date: 2020-02-26, Last modification date: 2024-11-06)

Primary citation

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.
Structure of the neurotensin receptor 1 in complex with beta-arrestin 1.
Nature, 579:303-308, 2020

PubMed Abstract: 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. 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.

PubMed: 31945771
DOI: 10.1038/s41586-020-1953-1

Experimental method

ELECTRON MICROSCOPY (4.2 Å)