Noncooperative Dimethyl Sulfoxide-Induced Dissection of Insulin Fibrils: Toward Soluble Building Blocks of Amyloid

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• 作者：Anna Loksztejn ; Wojciech Dzwolak
• 刊名：Biochemistry
• 出版年：2009
• 出版时间：June 9, 2009
• 年：2009
• 卷：48
• 期：22
• 页码：4846-4851
• 全文大小：914K
• 年卷期：v.48,no.22(June 9, 2009)
• ISSN：1520-4995

文摘

The enormous molecular weight complicates detailed structural studies of amyloid fibrils and obscures identification of biologically active forms of protein aggregates in amyloid-related diseases. Here we show that aqueous solutions of dimethyl sulfoxide (DMSO) solubilize insulin fibrils while maintaining their β-pleated structure. This is accompanied by a marked decrease in the fluorescence of thioflavin T. According to atomic force microscopy images and dynamic light scattering measurements, the partial DMSO-induced dissection of insulin fibrils favors formation of smaller soluble oligomers, which retain a limited capacity to induce daughter generation of fibrils through seeding to the native insulin, as well as the ability to reassemble into fibrils upon removal of DMSO through dialysis against water. These findings suggest that the DMSO-induced ensembles of insulin molecules are closely related to elementary building blocks of amyloid fibrils.