Department of Integrative Structural and Computational Biology and Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA.
Department of Integrative Structural and Computational Biology and Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA.
Curr Opin Struct Biol. 2021 Oct;70:44-52. doi: 10.1016/j.sbi.2021.03.015. Epub 2021 May 2.
Nuclear magnetic resonance (NMR) has long been instrumental in the characterization of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs). This method continues to offer rich insights into the nature of IDPs in solution, especially in combination with other biophysical methods such as small-angle scattering, single-molecule fluorescence, electron paramagnetic resonance (EPR), and mass spectrometry. Substantial advances have been made in recent years in studies of proteins containing both ordered and disordered domains and in the characterization of problematic sequences containing repeated tracts of a single or a few amino acids. These sequences are relevant to disease states such as Alzheimer's, Parkinson's, and Huntington's diseases, where disordered proteins misfold into harmful amyloid. Innovative applications of NMR are providing novel insights into mechanisms of protein aggregation and the complexity of IDP interactions with their targets. As a basis for understanding the solution structural ensembles, dynamic behavior, and functional mechanisms of IDPs and IDRs, NMR continues to prove invaluable.
核磁共振（NMR）长期以来一直是研究无规卷曲蛋白质（IDP）和无规卷曲区域（IDR）的重要工具。该方法继续为了解 IDP 在溶液中的性质提供了丰富的见解，特别是与其他生物物理方法（如小角散射、单分子荧光、电子顺磁共振（EPR）和质谱）结合使用时。近年来，在研究包含有序和无序结构域的蛋白质以及对含有单个或少数氨基酸重复片段的有问题序列的表征方面取得了重大进展。这些序列与阿尔茨海默病、帕金森病和亨廷顿病等疾病状态有关，其中无序蛋白质错误折叠成有害的淀粉样蛋白。NMR 的创新应用为蛋白质聚集机制以及 IDP 与靶标的相互作用的复杂性提供了新的见解。作为理解 IDP 和 IDR 的溶液结构集合、动态行为和功能机制的基础，NMR 继续证明是非常宝贵的。
