The last ∼25 years has seen mass spectrometry (MS) emerge as an integral method in the structural biology toolkit. In particular, MS has enabled the structural characterization of proteins and protein assemblies that have been intractable by other methods, especially those that are large, heterogeneous or transient, providing experimental evidence for their structural organization in support of, and in advance of, high resolution methods. The most recent frontier conquered in the field of MS-based structural biology has been the application of established methods for studying water soluble proteins to the more challenging targets of integral membrane proteins. The power of MS in obtaining structural information has been enabled by advances in instrumentation and the development of hyphenated mass spectrometry-based methods, such as ion mobility spectrometry-MS, chemical crosslinking-MS and other chemical labelling/footprinting-MS methods. In this review we detail the insights garnered into the structural biology of membrane proteins by applying such techniques. Application and refinement of these methods has yielded unprecedented insights in many areas, including membrane protein conformation, dynamics, lipid/ligand binding, and conformational perturbations due to ligand binding, which can be challenging to study using other methods.

中文翻译：

---

质谱支持的膜蛋白结构生物学

在过去的 25 年里，质谱 (MS) 成为结构生物学工具包中不可或缺的方法。特别是，MS 使其他方法难以处理的蛋白质和蛋白质组件的结构表征成为可能，尤其是那些大的、异质的或瞬态的，为其结构组织提供实验证据，支持并提前实现高分辨率方法。在基于 MS 的结构生物学领域中征服的最新前沿是将研究水溶性蛋白质的既定方法应用于更具挑战性的膜蛋白靶标。仪器的进步和基于联用质谱的方法的发展使 MS 在获取结构信息方面的能力成为可能，例如离子迁移谱-MS、化学交联-MS和其他化学标记/足迹-MS方法。在这篇综述中，我们详细介绍了通过应用这些技术获得的膜蛋白结构生物学的见解。这些方法的应用和改进在许多领域产生了前所未有的见解，包括膜蛋白构象、动力学、脂质/配体结合以及由于配体结合引起的构象扰动，使用其他方法进行研究可能具有挑战性。