Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA.
FEBS Lett. 2013 Apr 17;587(8):1096-105. doi: 10.1016/j.febslet.2013.02.044. Epub 2013 Mar 1.
Several widespread and severe degenerative diseases are characterized by the deposition of amyloid protein aggregates in affected tissues. While there is great interest in the complete description of the aggregation pathway of the proteins involved, a molecular level understanding is hindered by the complexity of the self-assembly process. In particular, the early stages of aggregation, where dynamic, heterogeneous and often toxic intermediates are populated, are resistant to high-resolution structural characterization. Fluorescence spectroscopy is a powerful and versatile tool for such analysis. In this review, we survey its application to provide residue-specific information about amyloid intermediate states for three selected proteins: IAPP, α-synuclein, and tau.
几种广泛而严重的退行性疾病的特征是在受影响的组织中沉积淀粉样蛋白聚集物。虽然人们对参与的蛋白质的聚合途径的完整描述很感兴趣，但由于自组装过程的复杂性，对其分子水平的理解受到了阻碍。特别是在聚合的早期阶段，充满了动态的、异质的且往往有毒的中间体，这使得它们无法进行高分辨率的结构特征描述。荧光光谱是进行这种分析的强大而通用的工具。在这篇综述中，我们调查了它的应用，为三种选定的蛋白质：IAPP、α-突触核蛋白和 tau，提供了关于淀粉样蛋白中间状态的残基特异性信息。
