Proteins often undergo large-scale conformational transitions, in which secondary and tertiary structure elements (loops, helices, and domains) change their structures or their positions with respect to each other. Simple considerations suggest that such dynamics should be relatively fast, but the functional cycles of many proteins are often relatively slow. Sophisticated experimental methods are starting to tackle this dichotomy and shed light on the contribution of large-scale conformational dynamics to protein function. In this review, we focus on the contribution of single-molecule Förster resonance energy transfer and nuclear magnetic resonance (NMR) spectroscopies to the study of conformational dynamics. We briefly describe the state of the art in each of each of these techniques and then point out their similarities and differences, as well as the relative strengths and weaknesses of each. Several case studies, in which the connection between fast conformational dynamics and slower function has been demonstrated, are then introduced and discussed. These examples include both enzymes and large protein machines, some of which have been studied by both NMR and fluorescence spectroscopies.Expected final online publication date for the Annual Review of Biophysics, Volume 53 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

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NMR 和单分子 FRET 深入了解蛋白质快速运动及其与功能的关系

蛋白质经常经历大规模构象转变，其中二级和三级结构元件（环、螺旋和结构域）改变其结构或相对于彼此的位置。简单的考虑表明，这种动态应该相对较快，但许多蛋白质的功能循环通常相对较慢。复杂的实验方法开始解决这种二分法，并揭示大规模构象动力学对蛋白质功能的贡献。在这篇综述中，我们重点关注单分子福斯特共振能量转移和核磁共振（NMR）波谱对构象动力学研究的贡献。我们简要描述每种技术的最新技术，然后指出它们的相似点和差异，以及每种技术的相对优势和劣势。然后介绍和讨论了几个案例研究，其中证明了快速构象动力学与较慢功能之间的联系。这些例子包括酶和大型蛋白质机器，其中一些已经通过核磁共振和荧光光谱进行了研究。《生物物理学年度评论》第 53 卷的预计最终在线出版日期为 2024 年 5 月。请参阅 http://www.annualreviews .org/page/journal/pubdates 了解修订后的估计。