title: Hexafluoroisopropanol induces amyloid fibrils of islet amyloid polypeptide by enhancing both hydrophobic and electrostatic interactions.
abstract: 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.
authors.affiliation: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yanagi
authors.forename: Mizue
authors.initials: M
authors.lastname: Ashizaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yagi
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Sakurai
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D052160:Benzothiazoles; D006801:Humans; D006863:Hydrogen-Ion Concentration; D058228:Islet Amyloid Polypeptide / Q000737:chemistry*; D020005:Propanols / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D055672:Static Electricity; D013844:Thiazoles / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D058228:Islet Amyloid Polypeptide; D020005:Propanols; D013844:Thiazoles; C009462:thioflavin T; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated