Increasing evidence suggests that most proteins occur and function in complexes rather than as isolated entities when embedded in cellular membranes. Nuclear magnetic resonance (NMR) provides increasing possibilities to study structure, dynamics and assembly of such systems. In our review, we discuss recent methodological progress to study membrane–protein complexes (MPCs) by NMR, starting with expression, isotope-labeling and reconstitution protocols. We review approaches to deal with spectral complexity and limited spectral spectroscopic sensitivity that are usually encountered in NMR-based studies of MPCs. We highlight NMR applications in various classes of MPCs, including G-protein-coupled receptors, ion channels and retinal proteins and extend our discussion to protein–protein complexes that span entire cellular compartments or orchestrate processes such as protein transport across or within membranes. These examples demonstrate the growing potential of NMR-based studies of MPCs to provide critical insight into the energetics of protein–ligand and protein–protein interactions that underlie essential biological functions in cellular membranes.

中文翻译：

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核磁共振 (NMR) 应用于膜蛋白复合物

越来越多的证据表明，当嵌入细胞膜时，大多数蛋白质以复合物的形式出现和发挥作用，而不是作为孤立的实体。核磁共振 (NMR) 为研究此类系统的结构、动力学和组装提供了越来越多的可能性。在我们的综述中，我们讨论了最近通过 NMR 研究膜蛋白复合物 (MPC) 的方法学进展，从表达、同位素标记和重组方案开始。我们回顾了处理基于 NMR 的 MPC 研究中通常遇到的光谱复杂性和有限的光谱光谱灵敏度的方法。我们重点介绍 NMR 在各类 MPC 中的应用，包括 G 蛋白偶联受体、离子通道和视网膜蛋白，并将我们的讨论扩展到跨越整个细胞区室或协调过程的蛋白质 - 蛋白质复合物，例如跨膜或膜内的蛋白质转运。这些例子证明了基于 NMR 的 MPC 研究的日益增长的潜力，以提供对蛋白质-配体和蛋白质-蛋白质相互作用的能量学的重要见解，这些相互作用是细胞膜中基本生物学功能的基础。