Hexafluoroisopropanol induces amyloid fibrils of islet amyloid polypeptide by enhancing both hydrophobic and electrostatic interactions

• Yanagi, Kotaro

• Ashizaki, Mizue

• Yagi, Hisashi

• Sakurai, Kazumasa

• Lee, Young-Ho

• Goto, Yuji

抄録

This research was originally published in the Journal of Biological Chemistry. Kotaro Yanagi, Mizue Ashizaki, Hisashi Yagi, Kazumasa Sakurai, Young-Ho Lee and Yuji Goto. Hexafluoroisopropanol Induces Amyloid Fibrils of Islet Amyloid Polypeptide by Enhancing Both Hydrophobic and Electrostatic Interactions. J. Biol. Chem. 2011; 286, 23959-23966. © the American Society for Biochemistry and Molecular Biology

Although amyloid fibrils deposit with various proteins, the comprehensive mechanism by which they form remains unclear. We studied the formation of fibrils of human islet amyloid polypeptide associated with type II diabetes in the presence of various concentrations of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) under acidic and neutral pH conditions using CD, amyloid-specific thioflavin T fluorescence, fluorescence imaging with thioflavin T, and atomic force microscopy. At low pH, the formation of fibrils was promoted by HFIP with an optimum at 5% (v/v). At neutral pH in the absence of HFIP, significant amounts of amorphous aggregates formed in addition to the fibrils. The addition of HFIP suppressed the formation of amorphous aggregates, leading to a predominance of fibrils with an optimum effect at 25% (v/v). Under both conditions, higher concentrations of HFIP dissolved the fibrils and stabilized the α-helical structure. The results indicate that fibrils and amorphous aggregates are different types of precipitates formed by exclusion from water-HFIP mixtures. The exclusion occurs through the combined effects of hydrophobic interactions and electrostatic interactions, both of which are strengthened by low concentrations of HFIP, and a subtle balance between the two types of interactions determines whether the fibrils or amorphous aggregates dominate. We suggest a general view of how the structure of precipitates varies dramatically from single crystals to amyloid fibrils and amorphous aggregates.

収録刊行物

• Journal of Biological Chemistry

  Journal of Biological Chemistry 286 (27), 23959-23966, 2011-07

  American Society for Biochemistry and Molecular Biology

詳細情報

• CRID: 1050018218948928000
• NII論文ID: 120006557643
• NII書誌ID: AA1202452X
• ISSN: 1083351X
• HANDLE: 11094/71283
• 本文言語コード: en
• 資料種別: journal article
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