在脂质纳米盘中M2肌酸受体-β-arrestin复合体的结构
Dean P Staus1,2, Hongli Hu3,4, Michael J Robertson3,5
1Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Nature
|January 17, 2020
概括
研究人员透露了使用冷EM的β-arrestin1如何与G蛋白合受体 (GPCR) 相互作用. 这种涉及受体和脂质双层的相互作用是受体内化和信号脱敏的关键.
科学领域:
- 结构生物学
- 细胞信号传输
- 生物物理
背景情况:
- G蛋白结合受体 (GPCRs) 激活信号通路,并调用β-arrestin进行脱敏和内细胞分裂.
- 与G蛋白相互作用不同的是,β-arrestin与GPCR相互作用的分子机制尚不清楚.
研究的目的:
- 阐明β-arrestin 1 (βarr1) 与M2肌酸受体 (M2R) 的相互作用的结构基础.
- 了解βarr1与受体和脂质双层在细胞反应中的作用.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定纳米盘中的M2R-βarr1复合物的结构.
- 原子模拟,生物物理,生物化学和细胞测试以验证功能作用.
主要成果:
- 一个冷EM结构揭示了βarr1和M2R之间的多模式相互作用网络,包括N-域结合和指环插入.
- 观察到βarr1的C边缘参与了脂质双层,这是复杂稳定性和功能的关键相互作用.
- 这种相互作用对于βarr1招募,受体内化和G蛋白脱敏是必不可少的.
结论:
- β-arrestin 1 使用与GPCR和脂质双层的多功能相互作用网络.
- 与受体和膜的合作结合对于β-arrestin的多种信号作用和GPCR活性的调节至关重要.
相关概念视频
Fluid Mosaic Model
15.4K
Scientists identified the plasma membrane in the 1890s and its principal chemical components (lipids and proteins) by 1915. The model for plasma membrane structure, proposed in 1935 by Hugh Davson and James Danielli, was the first model to be widely accepted in the scientific community. The model was based on the plasma membrane's "railroad track" appearance in early electron micrographs. Davson and Danielli theorized that the plasma membrane's structure resembled a sandwich...
15.4K
Assembly of Signaling Complexes
6.4K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.4K
Cholinergic Receptors: Muscarinic
4.5K
The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....
4.5K
Cholinergic Receptors: Nicotinic
5.1K
Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
5.1K


