The impact of protein disulfide bonds on the amyloid fibril morphology.
The impact of protein disulfide bonds on the amyloid fibril morphology.
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DOI：
10.1504/ijbnn.2011.041000
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发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Lednev, Igor K
中科院分区：
文献类型：
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作者：
Kurouski, Dmitry;Lednev, Igor K
淀粉样原纤维与许多神经退行性疾病有关。淀粉样蛋白原纤维由20多种功能或结构上不相关的不同蛋白质形成，具有共同的交叉β核心结构。一个广为人知的假设是，原纤维的生物活性和相关毒性随其形态而变化。天然蛋白质的部分变性通常先于原纤化的初始阶段，即成核过程。低pH值和升高的温度，淀粉样蛋白原纤维在体外形成的典型条件，导致蛋白质的部分变性。二硫键的裂解通常导致蛋白质天然结构的显著破坏和熔融整体状态的形成。在这里，我们报告的原纤维形成的apo-alpha-乳白蛋白和它的类似物，只包含一个原始的四个二硫键，使用深紫外共振和非共振拉曼光谱和原子力显微镜的比较调查。在聚集机制和由此产生的原纤维形态的显着差异被发现。
Amyloid fibrils are associated with many neurodegenerative diseases. Being formed from more than 20 different proteins that are functionally or structurally unrelated, amyloid fibrils share a common cross-beta core structure. It is a well-accepted hypothesis that fibril biological activity and the associated toxicity vary with their morphology. Partial denaturation of a native protein usually precedes the initial stage of fibrillation, namely the nucleation process. Low pH and elevated temperature, typical conditions of amyloid fibril formation in vitro, resulted in partial denaturation of the proteins. Cleavage of disulfide bonds results typically in significant disruption of protein native structure and in the formation of the molten global state. Herein we report on a comparative investigation of fibril formation by apo-alpha-lactalbumin and its analog that contains only one of the four original disulfide bonds using deep UV resonance and non-resonance Raman spectroscopy and atomic force microscopy. Significant differences in the aggregation mechanism and the resulting fibril morphology were found.