Illuminating GPCR signaling mechanisms by NMR spectroscopy with stable-isotope labeled receptors

IF 4 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Beining Jin, Naveen Thakur, Anuradha V. Wijesekara, Matthew T. Eddy
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引用次数: 1

Abstract

G protein-coupled receptors (GPCRs) exhibit remarkable structural plasticity, which underlies their capacity to recognize a wide range of extracellular molecules and interact with intracellular partner proteins. Nuclear magnetic resonance (NMR) spectroscopy is uniquely well-suited to investigate GPCR structural plasticity, enabled by stable-isotope “probes” incorporated into receptors that inform on structure and dynamics. Progress with stable-isotope labeling methods in Eukaryotic expression systems has enabled production of native or nearly-native human receptors with varied and complementary distributions of NMR probes. These advances have opened up new avenues for investigating the roles of conformational dynamics in signaling processes, including by mapping allosteric communication networks, understanding the specificity of GPCR interactions with partner proteins and exploring the impact of membrane environments on GPCR function.

Abstract Image

用稳定同位素标记的受体通过NMR光谱阐明GPCR信号机制。
G蛋白偶联受体(GPCR)表现出显著的结构可塑性,这是其识别多种细胞外分子并与细胞内伴侣蛋白相互作用的能力的基础。核磁共振(NMR)光谱特别适合研究GPCR的结构可塑性,这是由结合到受体中的稳定同位素“探针”实现的,这些探针可以提供结构和动力学信息。在真核表达系统中稳定同位素标记方法的进展使得能够产生具有不同和互补分布的NMR探针的天然或几乎天然的人类受体。这些进展为研究构象动力学在信号传导过程中的作用开辟了新的途径,包括绘制变构通信网络,了解GPCR与伴侣蛋白相互作用的特异性,以及探索膜环境对GPCR功能的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.80
自引率
2.50%
发文量
131
审稿时长
4-8 weeks
期刊介绍: Current Opinion in Pharmacology (COPHAR) publishes authoritative, comprehensive, and systematic reviews. COPHAR helps specialists keep up to date with a clear and readable synthesis on current advances in pharmacology and drug discovery. Expert authors annotate the most interesting papers from the expanding volume of information published today, saving valuable time and giving the reader insight on areas of importance.
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