Membrane proteins fulfil a plethora of vital functions, are major drug targets, and are implicated in many diseases. Their importance, however, is in no way paralleled by our current understanding of the dynamic processes by which these proteins fold into and function within cellular membranes. This is mainly due to fundamental challenges in resolving the structural dynamics of proteins embedded within lipid-bilayer membranes or membrane-mimetic environments. Single-molecule spectroscopy bears great potential for dissecting this complexity. Particularly, single-molecule Förster resonance energy transfer (smFRET), owing to its sensitivity and versatility, has emerged as a new tool for accessing the spatial, temporal, and energetic features of membrane-protein folding reactions, providing unique insights into protein subpopulations and their associated dynamics on timescales ranging from nanoseconds to hours. Here, we review recent advances in the application of smFRET to the structural dynamics of membrane-protein folding and discuss the benefits that this new toolset affords to provide a molecular-level description of the dynamics governing this physiologically and therapeutically eminent class of proteins.

中文翻译：

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单分子FRET膜蛋白折叠的结构动力学。

膜蛋白具有多种重要功能，是主要的药物靶标，与多种疾病有关。但是，它们的重要性与我们目前对这些蛋白质折叠进入细胞膜并在细胞膜中发挥作用的动态过程的理解没有任何平行之处。这主要是由于解决脂双层膜或拟膜环境中嵌入的蛋白质的结构动力学方面的根本挑战。单分子光谱法具有剖析这种复杂性的巨大潜力。特别是由于其灵敏度和多功能性，单分子Förster共振能量转移（smFRET）已成为一种获取膜蛋白折叠反应的空间，时间和能量特征的新工具，提供从纳秒到几小时的时间尺度上蛋白质亚群及其相关动力学的独特见解。在这里，我们回顾了smFRET在膜蛋白折叠结构动力学中应用的最新进展，并讨论了该新工具集所提供的益处，从而提供了在分子水平上描述这种在生理和治疗上都非常重要的蛋白动力学的描述。