Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, 77843, US.
Department of Biotechnology, Binh Duong University, Thu Dau Mot, 820000, Vietnam.
Chembiochem. 2020 Feb 17;21(4):481-485. doi: 10.1002/cbic.201900394. Epub 2019 Oct 8.
Spontaneous aggregation of misfolded proteins typically results in the formation of morphologically and structurally different amyloid fibrils, protein aggregates that are strongly associated with various neurodegenerative disorders. Elucidation of the structural organization of amyloid aggregates is crucial to understanding their role in the onset and progression of these diseases. Using atomic force microscopy-infrared spectroscopy (AFM-IR), we investigated the structural organization of insulin fibrils. We found that insulin aggregation results in the formation of two structurally different fibril polymorphs. One polymorph has a β-sheet core surrounded by primarily unordered protein secondary structure. This polymorph has β-sheet-rich surface, whereas the surface of the other fibril polymorph is primarily composed of unordered protein. Using AFM-IR, we also revealed the structural organization of the insulin oligomers. Finally, we discovered a new pathway for amyloid fibril formation that is based on a fusion of several oligomers into a single fibril structure.
错误折叠蛋白质的自发聚集通常会导致形态和结构不同的淀粉样纤维的形成，这些蛋白质聚集体与各种神经退行性疾病密切相关。阐明淀粉样聚集物的结构组织对于理解它们在这些疾病的发生和进展中的作用至关重要。使用原子力显微镜-红外光谱（AFM-IR），我们研究了胰岛素纤维的结构组织。我们发现，胰岛素聚集导致两种结构不同的纤维态的形成。一种纤维态具有β-折叠核心，周围主要是无规卷曲的蛋白质二级结构。这种纤维态具有富含β-折叠的表面，而另一种纤维态的表面主要由无规卷曲的蛋白质组成。使用 AFM-IR，我们还揭示了胰岛素低聚物的结构组织。最后，我们发现了一种新的淀粉样纤维形成途径，该途径基于几个低聚物融合成单个纤维结构。
