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Identifying Insulin Fibril Conformational Differences by Thioflavin-T Binding Characteristics
Biomacromolecules ( IF 6.2 ) Pub Date : 2020-11-17 , DOI: 10.1021/acs.biomac.0c01178
Mantas Ziaunys 1 , Andrius Sakalauskas 1 , Vytautas Smirnovas 1
Affiliation  

Amyloidogenic protein aggregation into highly structured fibrils is linked to more than 30 amyloidoses, including several neurodegenerative disorders. Despite significant progress in trying to understand the process of amyloid formation, there is still no cure or effective treatment available. A number of studies involving potential anti-amyloid compounds rely on the use of a fluorescent probe—thioflavin-T—to track the appearance, growth, or disassembly of these cytotoxic aggregates. Despite the wide application of this dye molecule, its interaction with amyloid fibrils is still poorly understood. Recent reports have shown it may possess distinct binding modes and fluorescence intensities based on the conformation of the examined fibrils. In this work, we generate insulin fibrils under four different conditions and attempt to identify distinct conformations using both classic methods, such as atomic force microscopy and Fourier-transform infrared spectroscopy, as well as their ThT binding ability and fluorescence quantum yield. We show that there is a significant variance of ThT fluorescence quantum yields, excitation/emission maxima positions, and binding modes between distinct insulin fibril conformations.

中文翻译:

通过硫黄素-T结合特征鉴定胰岛素原纤维构象差异

淀粉样蛋白生成的蛋白质聚集成高度结构化的原纤维与30多种淀粉样糖有关,包括几种神经退行性疾病。尽管在试图了解淀粉样蛋白形成过程方面取得了重大进展,但是仍然没有治愈或有效的治疗方法。涉及潜在的抗淀粉样蛋白化合物的许多研究都依赖于使用荧光探针thioflavin-T来追踪这些细胞毒性聚集体的出现,生长或分解。尽管该染料分子得到了广泛的应用,但其与淀粉样蛋白原纤维的相互作用仍知之甚少。最近的报道表明,根据所检查的原纤维的构象,它可能具有独特的结合模式和荧光强度。在这项工作中 我们在四种不同条件下生成胰岛素原纤维,并尝试使用两种经典方法(例如原子力显微镜和傅里叶变换红外光谱法)以及它们的ThT结合能力和荧光量子产率来鉴定不同的构象。我们表明,ThT荧光量子产率,激发/发射最大值位置以及不同胰岛素原纤维构象之间的结合模式存在显着差异。
更新日期:2020-12-14
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