Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
Department of Chemistry, King's College London, London, UK.
Protein Sci. 2020 Jun;29(6):1285-1301. doi: 10.1002/pro.3853. Epub 2020 Mar 25.
Integral membrane proteins (IMPs) control countless fundamental biological processes and constitute the majority of drug targets. For this reason, uncovering their molecular mechanism of action has long been an intense field of research. They are, however, notoriously difficult to work with, mainly due to their localization within the heterogeneous of environment of the biological membrane and the instability once extracted from the lipid bilayer. High-resolution structures have unveiled many mechanistic aspects of IMPs but also revealed that the elucidation of static pictures has limitations. Hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) has recently emerged as a powerful biophysical tool for interrogating the conformational dynamics of proteins and their interactions with ligands. Its versatility has proven particularly useful to reveal mechanistic aspects of challenging classes of proteins such as IMPs. This review recapitulates the accomplishments of HDX-MS as it has matured into an essential tool for membrane protein structural biologists.
整合膜蛋白（IMP）控制着无数基本的生物过程，并且构成了大多数药物靶点。出于这个原因，揭示它们的作用机制一直是一个激烈的研究领域。然而，由于它们在生物膜异质环境中的定位以及从脂质双层中提取后的不稳定性，IMP 非常难以研究。高分辨率结构揭示了 IMP 的许多机械方面，但也表明阐明静态图片具有局限性。氢氘交换与质谱（HDX-MS）的结合最近已成为一种强大的生物物理工具，可用于研究蛋白质的构象动力学及其与配体的相互作用。其多功能性已被证明对揭示具有挑战性的蛋白质（如 IMP）的机械方面特别有用。这篇综述回顾了 HDX-MS 的成就，因为它已经成熟为膜蛋白结构生物学家的重要工具。
