Abstract：
Solvent paramagnetic relaxation enhancement (sPRE) is a versatile nuclear magnetic resonance (NMR)-based method that allows characterization of the structure and dynamics of biomolecular systems through providing quantitative experimental information on solvent accessibility of NMR-active nuclei. Addition of soluble paramagnetic probes to the solution of a biomolecule leads to paramagnetic relaxation enhancement in a concentration-dependent manner. Here we review recent progress in the sPRE-based characterization of structural and dynamic properties of biomolecules and their complexes, and aim to deliver a comprehensive illustration of a growing number of applications of the method to various biological systems. We discuss the physical principles of sPRE measurements and provide an overview of available co-solute paramagnetic probes. We then explore how sPRE, in combination with complementary biophysical techniques, can further advance biomolecular structure determination, identification of interaction surfaces within protein complexes, and probing of conformational changes and low-population transient states, as well as deliver insights into weak, nonspecific, and transient interactions between proteins and co-solutes. In addition, we present examples of how the incorporation of solvent paramagnetic probes can improve the sensitivity of NMR experiments and discuss the prospects of applying sPRE to NMR metabolomics, drug discovery, and the study of intrinsically disordered proteins.
摘要：
溶剂顺磁弛豫增强（sPRE）是一种基于核磁共振（NMR）的通用方法，可通过提供有关NMR活性核的溶剂可达性的定量实验信息来表征生物分子系统的结构和动力学。将可溶性顺磁探针添加到生物分子的溶液中以浓度依赖性方式导致顺磁弛豫增强。在这里，我们回顾了基于sPRE的生物分子及其复合物的结构和动态性质表征的最新进展，并且旨在提供该方法在各种生物系统中越来越多的应用的全面说明。我们讨论了sPRE测量的物理原理，并提供了可用的共溶质顺磁探针的概述。然后我们探索如何SPRE，结合互补的生物物理技术，可以进一步推进生物分子结构的测定，鉴定蛋白质复合物内的相互作用表面，以及构象变化和低种群瞬态的探测，以及提供对弱者的见解，非特异性,以及蛋白质和共溶质之间的瞬时相互作用。此外,我们介绍了溶剂顺磁探针的掺入如何提高NMR实验的灵敏度，并讨论了将SPRE应用于NMR代谢组学的前景。药物发现,以及对内在无序蛋白质的研究。
