The role of protein stability, solubility, and net charge in amyloid fibril formation

Authors

  • Jason P. Schmittschmitt,

    1. Department of Biochemistry and Biophysics, Center for Advanced Biomolecular Research, Texas A&M University, College Station, Texas 77843-1114, USA
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  • J. Martin Scholtz

    Corresponding author
    1. Department of Biochemistry and Biophysics, Center for Advanced Biomolecular Research, Texas A&M University, College Station, Texas 77843-1114, USA
    2. Department of Medical Biochemistry and Genetics, Center for Advanced Biomolecular Research, Texas A&M University, College Station, Texas 77843-1114, USA
    • Department of Biochemistry and Biophysics, Center for Advanced Biomolecular Research, Texas A&M University, College Station, TX 77843-1114, USA; fax: (979) 847-9481.
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Abstract

Ribonuclease Sa and two charge-reversal variants can be converted into amyloid in vitro by the addition of 2,2,2-triflouroethanol (TFE). We report here amyloid fibril formation for these proteins as a function of pH. The pH at maximal fibril formation correlates with the pH dependence of protein solubility, but not with stability, for these variants. Additionally, we show that the pH at maximal fibril formation for a number of well-characterized proteins is near the pI, where the protein is expected to be the least soluble. This suggests that protein solubility is an important determinant of fibril formation.

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