Solubility and Supersaturation-Dependent Protein Misfolding Revealed by Ultrasonication

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• 作者：Yuxi Lin ; Young-Ho Lee ; Yuichi Yoshimura ; Hisashi Yagi ; Yuji Goto
• 刊名：Langmuir
• 出版年：2014
• 出版时间：February 25, 2014
• 年：2014
• 卷：30
• 期：7
• 页码：1845-1854
• 全文大小：576K
• 年卷期：v.30,no.7(February 25, 2014)
• ISSN：1520-5827

文摘

Although alcohols are useful cosolvents for producing amyloid fibrils, the underlying mechanism of alcohol-dependent fibrillation is unclear. We studied the alcohol-induced fibrillation of hen egg-white lysozyme at various concentrations of ethanol, 2,2,2-trifluoroethanol (TFE), and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). Under the conditions where the alcohol-denatured lysozyme retained metastability, ultrasonication effectively triggered fibrillation. The optimal alcohol concentration depended on the alcohol species. HFIP showed a sharp maximum at 12鈥?6%. For TFE, a broad maximum at 40鈥?0% was observed. Ethanol exhibited only an increase in fibrillation above 60%. These profiles were opposite to the equilibrium solubility of lysozyme in water/alcohol mixtures. The results indicate that although fibrillation is determined by solubility, supersaturation prevents conformational transitions and ultrasonication is highly effective in minimizing an effect of supersaturation. We propose an alcohol-dependent protein misfolding funnel useful for examining amyloidogenicity. This misfolding funnel will apply to fibrillation under physiological conditions where biological environments play important roles in decreasing the solubility.