Structure and Dynamics of GPCRs in Lipid Membranes: Physical Principles and Experimental Approaches.

Structure and Dynamics of GPCRs in Lipid Membranes: Physical Principles and Experimental Approaches.
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DOI:
10.3390/molecules25204729
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发表时间:
2020-10-15
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Nietlispach D
Nietlispach D
中科院分区:
其他
文献类型:
--
作者:
Jones AJY;Gabriel F;Tandale A;Nietlispach D

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在过去的十年中,通过 GPCR 的结构和生物物理研究产生的大量信息为这些受体的复杂信号传导行为提供了前所未有的机制洞察。随着最近的信息激增,越来越明显的是,为了重现脂质和膜对这些变构受体的生物功能产生的各种影响,需要在充分接近天然脂质双层环境的条件下进行 GPCR 的体外研究。在本综述的第一部分中,我们评估了膜环境对脂质双层嵌入蛋白(例如 GPCR)产生的一些更普遍的影响。然后考虑更具体的效应,包括与特定脂质亚型的化学计量相互作用。在最后一部分中,我们调查了目前用于体外研究的一系列不同的膜模拟物,重点是 NMR 应用。
Over the past decade, the vast amount of information generated through structural and biophysical studies of GPCRs has provided unprecedented mechanistic insight into the complex signalling behaviour of these receptors. With this recent information surge, it has also become increasingly apparent that in order to reproduce the various effects that lipids and membranes exert on the biological function for these allosteric receptors, in vitro studies of GPCRs need to be conducted under conditions that adequately approximate the native lipid bilayer environment. In the first part of this review, we assess some of the more general effects that a membrane environment exerts on lipid bilayer-embedded proteins such as GPCRs. This is then followed by the consideration of more specific effects, including stoichiometric interactions with specific lipid subtypes. In the final section, we survey a range of different membrane mimetics that are currently used for in vitro studies, with a focus on NMR applications.
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