The role of NMR spectroscopy in mapping the conformational landscape of GPCRs
The role of NMR spectroscopy in mapping the conformational landscape of GPCRs
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DOI：
10.1016/j.sbi.2019.03.030
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发表时间：
2019-08-01
影响因子：
6.8
通讯作者：
Nietlispach, Daniel
中科院分区：
文献类型：
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作者：
Bostock, Mark J.;Solt, Andras S.;Nietlispach, Daniel
近年来，核磁共振（NMR）光谱已发展成为一个强大的机械工具，G蛋白偶联受体（GPCRs）的调查。NMR提供了支持这些重要受体的动态性质的见解，并揭示了在受体活化过程中探索的复杂构象能量景观的实验证据，从而导致信号传导。NMR研究突出了不同受体状态的动态特性以及活化过程中形成的交换途径和中间体，扩展了从其他技术获得的GPCR的静态视图。NMR研究可以在现实的膜样磷脂环境中进行，并且越来越多的标记策略选择提供了全面的受体范围的信息。结合其他结构方法，NMR有助于我们理解变构信号传播和GPCR与细胞内结合伴侣（IBP）的相互作用，这对解释细胞信号传导至关重要。
Over recent years, nuclear magnetic resonance (NMR) spectroscopy has developed into a powerful mechanistic tool for the investigation of G protein-coupled receptors (GPCRs). NMR provides insights which underpin the dynamic nature of these important receptors and reveals experimental evidence for a complex conformational energy landscape that is explored during receptor activation resulting in signalling. NMR studies have highlighted both the dynamic properties of different receptor states as well as the exchange pathways and intermediates formed during activation, extending the static view of GPCRs obtained from other techniques. NMR studies can be undertaken in realistic membrane-like phospholipid environments and an ever-increasing choice of labelling strategies provides comprehensive, receptor-wide information. Combined with other structural methods, NMR is contributing to our understanding of allosteric signal propagation and the interaction of GPCRs with intracellular binding partners (IBP), crucial to explaining cellular signalling.