German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, 37075, Göttingen, Germany.
Max Planck Institute for Multidisciplinary Sciences, Am Faßberg 11, 37077, Göttingen, Germany.
Angew Chem Int Ed Engl. 2023 Apr 17;62(17):e202218078. doi: 10.1002/anie.202218078. Epub 2023 Mar 15.
Liquid-Liquid phase separation has emerged as fundamental process underlying the formation of biomolecular condensates. Insights into the composition and structure of biomolecular condensates is, however, complicated by their molecular complexity and dynamics. Here, we introduce an improved spatially-resolved NMR experiment that enables quantitative analysis of the physico-chemical composition of multi-component biomolecular condensates in equilibrium and label-free. Application of spatially-resolved NMR to condensates formed by the Alzheimer's disease-associated protein Tau demonstrates decreased water content, exclusion of the molecular crowding agent dextran, presence of a specific chemical environment of the small molecule DSS, and ≈150-fold increased concentration of Tau inside the condensate. The results suggest that spatially-resolved NMR can have a major impact in understanding the composition and physical chemistry of biomolecular condensates.
液-液相分离已成为生物分子凝聚物形成的基本过程。然而，由于生物分子凝聚物的分子复杂性和动态性，对其组成和结构的了解变得复杂。在这里，我们介绍了一种改进的空间分辨 NMR 实验，该实验可实现对多组分生物分子凝聚物在平衡和无标记状态下的物理化学组成的定量分析。将空间分辨 NMR 应用于与阿尔茨海默病相关的蛋白 Tau 形成的凝聚物表明，水含量降低，分子拥挤剂葡聚糖被排除，小分子 DSS 的特定化学环境存在，并且 Tau 在凝聚物内部的浓度增加了约 150 倍。结果表明，空间分辨 NMR 可以在理解生物分子凝聚物的组成和物理化学性质方面产生重大影响。
