小柯机器人

美国斯坦福大学医学院Brian K. Kobilka、Georgios Skiniotis等研究人员合作解析了神经降压素受体1与β-arrestin1的复合物结构。相关论文2020年1月16日在线发表于《自然》。

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

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

Issue&Volume: 2020-01-16

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 pathways1,2. 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 β-arrestin 1 (βarr1ΔCT). We found that phosphorylation of NTSR1 was critical for obtaining a stable complex with βarr1ΔCT, 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° rotation of arrestin relative to the receptor. These findings highlight both conserved aspects but also the plasticity of arrestin–receptor interactions.

DOI: 10.1038/s41586-020-1953-1

Source: https://www.nature.com/articles/s41586-020-1953-1

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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