The present and future of solution NMR in investigating the structure and dynamics of channels and transporters.

The present and future of solution NMR in investigating the structure and dynamics of channels and transporters.
复制标题

溶液核磁共振在研究通道和转运体的结构和动力学方面的现状和未来。

DOI:
10.1016/j.sbi.2013.03.010
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发表时间:
2013
影响因子:
6.8
通讯作者:
Chou,JamesJ
Chou,JamesJ
中科院分区:
生物学2区
文献类型:
--
作者:
Oxenoid,Kirill;Chou,JamesJ

文献摘要

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概述了溶液核磁共振在完整膜蛋白结构表征中的成功应用。综述了核磁共振在研究离子通道的结构和动力学方面的进展。最新的核磁共振技术用于研究膜转运体。讨论了核磁共振在提供更动态的膜通道和转运体方面的前景。讨论了需要克服的技术挑战。膜通道、转运体和受体是细胞维持动态平衡和与环境沟通的重要手段。研究它们的分子结构和转运底物或通过膜屏障传递信号的动态过程一直是生物医学研究的前沿之一。在过去的十年中,X射线或电子结晶学在确定膜蛋白的原子分辨结构方面取得了许多成功,在某些情况下,甚至获得了同一蛋白质不同生理状态的快照。但也有许多情况下,长期的蛋白质结晶努力尚未成功。因此,我们有实际需要开发互补的生物物理工具,如核磁共振光谱学和电子显微镜来处理这些系统。本文提供了一些关键的例子,其中溶液核磁共振在提供离子通道和转运体的结构和功能信息方面起到了关键作用。
HighlightsOverview of successful applications of solution NMR in structural characterization of integral membrane proteins.Comprehensive review of the advancements in the use of NMR in investigating the structure and dynamics of ion channels.The latest NMR technology used to investigate membrane transporters.Discussion of the future prospects of NMR in providing more dynamic views of membrane channels and transporters.Discussion of the technical challenges to overcome.Membrane channels, transporters and receptors constitute essential means for cells to maintain homeostasis and communicate with the surroundings. Investigation of their molecular architecture and the dynamic process of transporting substrate or transmitting signals across the membrane barrier has been one of the frontiers in biomedical research. The past decade has seen numerous successes in the use of X-ray or electron crystallography in determining atomic-resolution structures of membrane proteins, and in some cases, even snapshots of different physiological states of the same protein have been obtained. But there are also many cases in which long-standing efforts to crystallize proteins have yet to succeed. Therefore we have practical needs for developing complementary biophysical tools such as NMR spectroscopy and electron microscopy for tackling these systems. This paper provides a number of key examples where the utility of solution NMR was pivotal in providing structural and functional information on ion channels and transporters.