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不计其数的结构时代的膜转运蛋白研究。

Membrane transporter research in times of countless structures.

机构信息

Institute of Medical Microbiology, University of Zurich, Switzerland.

出版信息

Biochim Biophys Acta Biomembr. 2018 Apr;1860(4):804-808. doi: 10.1016/j.bbamem.2017.08.009. Epub 2017 Aug 31.

Abstract

Structural biology has advanced our understanding of membrane proteins like no other scientific discipline in the past two decades and the number of high resolution membrane transporter structures solved by X-ray crystallography has increased exponentially over this time period. Currently, single particle cryo-EM is in full swing due to a recent resolution revolution and permits for structural insights of proteins that were refractory to crystallization. It is foreseeable that multiple structures of many human transporters will be solved in the coming five years. Nevertheless, many scientifically important questions remain unanswered despite of available structures, as is illustrated in this article at the example of multidrug efflux pumps and ABC transporters. Structure-function studies likely continue to be a supporting pillar of membrane transporter research. However, there is a trend towards the "integrated structural biologist", whose research focusses on a biological question and who closely collaborates with other research groups specialized in spectroscopy techniques or molecular dynamics simulation. Future membrane protein research requires joint efforts from specialists of various disciplines to finally work towards a molecular understanding of membrane transport in the context of the living cell. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain.

摘要

结构生物学在过去的二十年里极大地推动了我们对膜蛋白的理解,超过其他任何科学学科,在此期间,利用 X 射线晶体学解析的高分辨率膜转运蛋白结构呈指数增长。目前,由于最近的分辨率革命,单颗粒 cryo-EM 全面展开,并允许对以前无法结晶的蛋白质进行结构分析。可以预见,在未来五年内,许多人类转运蛋白的结构将得到解决。尽管有了这些结构,但仍有许多科学上重要的问题尚未得到解答,本文以多药外排泵和 ABC 转运蛋白为例说明了这一点。结构-功能研究可能仍然是膜转运蛋白研究的一个重要支柱。然而,现在有一种趋势是“综合结构生物学家”,他们的研究集中在一个生物学问题上,并与专门从事光谱技术或分子动力学模拟的其他研究小组密切合作。未来的膜蛋白研究需要来自各个学科的专家共同努力,最终在活细胞的背景下实现对膜转运的分子理解。本文是由 Ute Hellmich、Rupak Doshi 和 Benjamin McIlwain 编辑的特刊“超越膜蛋白的结构-功能视野”的一部分。

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