• melanin;
  • Pmel17;
  • repeat domains;
  • transmission electron microscopy;
  • tryptophan
Thumbnail image of graphical abstract

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.