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十年膜蛋白结构生物学的元分析:去污剂、膜模拟物和结构测定技术。

A 10-year meta-analysis of membrane protein structural biology: Detergents, membrane mimetics, and structure determination techniques.

机构信息

Department of Physiology and Cellular Biophysics, Columbia University, NY, NY, USA.

Department of Physiology and Cellular Biophysics, Columbia University, NY, NY, USA.

出版信息

Biochim Biophys Acta Biomembr. 2021 Mar 1;1863(3):183533. doi: 10.1016/j.bbamem.2020.183533. Epub 2020 Dec 17.

DOI:10.1016/j.bbamem.2020.183533
PMID:33340490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7856071/
Abstract

Structure determination of membrane proteins is critical to the molecular understanding of many life processes, yet it has historically been a technically challenging endeavor. This past decade has given rise to a number of technological advancements, techniques, and reagents, which have facilitated membrane protein structural biology, resulting in an ever-growing number of membrane protein structures determined. To collate these advances, we have mined available literature to analyze the purification and structure determination specifics for all uniquely solved membrane protein structures from 2010 to 2019. Our analyses demonstrate the strong impact of single-particle cryo-electron microscopy on the field and illustrate how this technique has affected detergent and membrane mimetic usage. Furthermore, we detail how different structure determination methods, taxonomic domains and protein classes have unique detergent/membrane mimetic profiles, highlighting the importance of tailoring their selection. Our analyses provide a quantitative overview of where the field of membrane protein structural biology stands and how it has developed over time. We anticipate that these will serve as a useful tool to streamline future membrane protein structure determination by guiding the choice of detergent/membrane mimetic.

摘要

膜蛋白结构的确定对于许多生命过程的分子理解至关重要,但在历史上,这一直是一项具有技术挑战性的工作。过去十年中出现了许多技术进步、技术和试剂,这些进步促进了膜蛋白结构生物学的发展,导致越来越多的膜蛋白结构得以确定。为了整理这些进展,我们挖掘了可用的文献,分析了 2010 年至 2019 年所有独特解决的膜蛋白结构的纯化和结构确定细节。我们的分析表明,单颗粒冷冻电子显微镜对该领域具有强大的影响,并说明了该技术如何影响去污剂和膜模拟物的使用。此外,我们详细介绍了不同的结构测定方法、分类单元和蛋白质类如何具有独特的去污剂/膜模拟物特征,突出了定制选择的重要性。我们的分析提供了膜蛋白结构生物学领域现状的定量概述,以及随着时间的推移它是如何发展的。我们预计,这些分析将通过指导去污剂/膜模拟物的选择,成为简化未来膜蛋白结构测定的有用工具。

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