Mechanism for retardation of amyloid fibril formation by sugars in Vλ6 protein

Authors

  • Masahiro Abe,

    1. Department of Protein Structure, Function and Design, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
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    • Masahiro Abe and Yoshito Abe contributed equally to this work.

  • Yoshito Abe,

    1. Department of Protein Structure, Function and Design, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
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    • Masahiro Abe and Yoshito Abe contributed equally to this work.

  • Takatoshi Ohkuri,

    1. Department of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
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  • Tomonori Mishima,

    1. Department of Protein Structure, Function and Design, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
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  • Akira Monji,

    1. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
    Current affiliation:
    1. Department of Psychiatry, Faculty of Medicine, Saga University, Japan
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  • Shigenobu Kanba,

    1. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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  • Tadashi Ueda

    Corresponding author
    1. Department of Protein Structure, Function and Design, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
    • Department of Protein Structure, Function and Design, Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
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Abstract

Sugars, which function as osmolytes within cells, retard the amyloid fibril formation of the amyloidosis peptides and proteins. To examine the mechanism of this retardation in detail, we analyzed the effect of sugars (trehalose, sucrose, and glucose) on the polypeptide chains in 3Hmut Wil, which is formed by the mutation of three His residues in Wil mutant as a cause of amyloid light-chain (AL) amyloidosis, at pH 2, a pH condition under which 3Hmut Wil was almost denatured. Sugars caused the folding of 3Hmut Wil so that its polypeptide chains adopted a native-like rather than a denatured conformation, as suggested by tryptophan fluorescence, CD spectroscopy, and heteronuclear NMR. Furthermore, these sugars promoted the folding to a native-like conformation according to the effect of preferential hydration rather than direct interaction. However, the type of sugar had no effect on the elongation of amyloid fibrils. Therefore, it was concluded that sugar affected the thermodynamic stability of 3Hmut Wil but not the elongation of amyloid fibrils.

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