Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134, Verona, Italy.
Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134, Verona, Italy.
Arch Biochem Biophys. 2020 Apr 15;683:108304. doi: 10.1016/j.abb.2020.108304. Epub 2020 Feb 22.
The extraordinary flexibility and structural heterogeneity of intrinsically disordered proteins (IDP) make them functionally versatile molecules. We have now begun to better understand their fundamental role in biology, however many aspects of their behaviour remain difficult to grasp experimentally. This is especially true for the intermolecular interactions which lead to the formation of transient or highly dynamic supramolecular self-assemblies, such as oligomers, aggregation intermediates and biomolecular condensates. Both the emerging functions and pathogenicity of these structures have stimulated great efforts to develop methodologies capable of providing useful insights. Significant progress in solution NMR spectroscopy has made this technique one of the most powerful to describe structural and dynamic features of IDPs within such assemblies at atomic resolution. Here, we review the most recent works that have illuminated key aspects of IDP assemblies and contributed significant advancements towards our understanding of the complex conformational landscape of prototypical disease-associated proteins. We also include a primer on some of the fundamental and innovative NMR methods being used in the discussed studies.
无定形蛋白质（IDP）的非凡灵活性和结构异质性使它们成为多功能分子。我们现在已经开始更好地理解它们在生物学中的基本作用，然而，它们的许多行为仍然难以通过实验来理解。对于导致瞬时或高度动态的超分子自组装形成的分子间相互作用尤其如此，例如寡聚体、聚集中间体和生物分子凝聚物。这些结构的新兴功能和致病性激发了开发能够提供有用见解的方法的巨大努力。溶液 NMR 光谱学的显著进展使该技术成为在原子分辨率下描述这些组装体中 IDP 的结构和动态特征的最强大技术之一。在这里，我们回顾了最近的一些研究工作，这些研究工作阐明了 IDP 组装的关键方面，并为我们理解与典型疾病相关蛋白质的复杂构象景观做出了重大贡献。我们还包括了一些基础和创新的 NMR 方法的介绍，这些方法在讨论的研究中得到了应用。
