与β-arrestin 1复合中的神经素受体1的结构
Weijiao Huang1, Matthieu Masureel1, Qianhui Qu1,2
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
Nature
|January 17, 2020
概括
研究人员阐明了激活G蛋白结合受体 (GPCRs) 的结构基础. 一个冷EM结构揭示了化神经素受体1 (NTSR1) 如何结合β-arrestin1,突出显示了保存和塑性相互作用.
科学领域:
- 结构生物学
- 分子药理学
- 细胞信号传输
背景情况:
- 通过阻断G蛋白合并启动受体内化,阿雷斯蛋白调节G蛋白合受体 (GPCR).
- 虽然GPCR-G蛋白相互作用已得到充分研究,但阿雷斯-GPCR参与的结构机制仍然不太清楚.
研究的目的:
- 确定与阿斯特林结合的化GPCR的高分辨率结构.
- 阐明阿斯特林-GPCR复合体形成的分子细节,并确定关键的相互作用部位.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 确定了人体全长神经素受体1 (NTSR1) 与截断的人类β-arrestin1 (βarr1 ((ΔCT)) 复合的结构.
主要成果:
- 化NTSR1对于βarr1 ((ΔCT) 的稳定复合体形成至关重要.
- 在NTSR1的细胞内循环和C终点中确定了特定的酸化位点作为潜在的相互作用媒介.
- 观察到一种酸盐-4,5-双酸盐分子在NTSR1和βarr1之间形成桥梁.
- 与其他阿斯特林-受体复合体相比,冷-EM结构显示了阿斯特林与受体的~85°旋转,表明了可塑性.
结论:
- 这项研究为阿斯特林与化GPCR,特别是NTSR1的结合提供了结构基础.
- 这些发现显示了阿雷斯-GPCR相互作用的保存性和适应性特征,这对于理解GPCR信号调节至关重要.
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