Cover Picture: Molecular Origin of pH-Dependent Fibril Formation of a Functional Amyloid (ChemBioChem 11/2014)

Authors

  • Dr. Ryan P. McGlinchey,

    1. Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892 (USA)
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  • Dr. Zhiping Jiang,

    1. Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892 (USA)
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  • Dr. Jennifer C. Lee

    Corresponding author
    1. Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892 (USA)
    • Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892 (USA)===

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Abstract

original image

The cover picture shows the reversible, pH-dependent fibril formation of the functional amyloid Pmel17 repeat domain. This unique polymerization process contrasts with that of disease-related amyloids, which resist the harshest of treatments, and thereby provides an effective way of controlling amyloid assembly. On p. 1569 ff., J. C. Lee et al. show that fibrils only form under mildly acidic pH (5±0.5) and completely dissolve at neutral pH. By using mutational analysis, it was determined that protonation of a single glutamic acid residue (out of the 16 carboxylic acids) is responsible for fibril formation and stability. Remarkably, removal of this single negative charge shifted the pH dependence by a full pH unit. Deprotonation of this residue results in intrasheet electrostatic repulsion and causes fibril dissolution at pH≥6.

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