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.

中文翻译：

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通过氢-氘交换质谱法了解完整膜蛋白的分子机理。

整体膜蛋白（IMP）控制着无数的基本生物学过程，并构成了大多数药物靶标。因此，揭示它们的分子作用机理一直是研究的热点。然而，众所周知，它们很难使用，主要是因为它们位于生物膜环境的异质环境中，并且一旦从脂质双层提取后就不稳定。高分辨率结构揭示了IMP的许多机理方面，但同时也揭示了静态图片的阐明是有局限性的。氢-氘交换与质谱（HDX-MS）耦合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。事实证明，它的多功能性对于揭示具有挑战性的蛋白质（例如IMPs）的机理方面特别有用。这篇综述概括了HDX-MS的成就，因为它已成为膜蛋白结构生物学家必不可少的工具。