ZFIN ID: ZDB-PUB-101222-15
Repeat Domains of Melanosome Matrix Protein Pmel17 Orthologs Form Amyloid Fibrils at the Acidic Melanosomal pH
McGlinchey, R.P., Shewmaker, F., Hu, K.N., McPhie, P., Tycko, R., and Wickner, R.B.
Date: 2011
Source: The Journal of biological chemistry 286(10): 8385-8393 (Journal)
Registered Authors:
Keywords: Amyloid, Electron microscopy (EM), NMR, Protein assembly, Protein folding, Protein structure, melanosome
MeSH Terms:
  • Amyloid/chemistry
  • Amyloid/genetics
  • Amyloid/metabolism*
  • Animals
  • Humans
  • Hydrogen-Ion Concentration
  • Mice
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Zebrafish
  • gp100 Melanoma Antigen/chemistry
  • gp100 Melanoma Antigen/genetics
  • gp100 Melanoma Antigen/metabolism*
PubMed: 21148556 Full text @ J. Biol. Chem.
ABSTRACT
Most amyloids are pathological, but fragments of Pmel17 form a functional amyloid in vertebrate melanosomes essential for melanin synthesis and deposition. We previously reported that only at the mildly acidic pH (4-5.5) typical of melanosomes, the repeat domain (RPT) of human Pmel17 can form amyloid in vitro. Combined with the known presence of RPT in the melanosome filaments and the requirement of this domain for filament formation, we proposed that RPT may be the core of the amyloid formed in vivo. While most of Pmel17 is highly conserved across a broad range of vertebrates, the RPT domains vary dramatically, with no apparent homology in some cases. Here we report that the RPT domains of mouse and zebrafish, as well as a small splice variant of human Pmel17 all form amyloid specifically at mildly acid pH (pH ~5.0). Protease digestion, mass per unit length measurements and solid-state NMR experiments suggest that amyloid of the mouse RPT has an in-register parallel β-sheet architecture with two RPT molecules per layer, similar to amyloid of Aβ peptide. Although there is no sequence conservation between human and zebrafish RPT, amyloid formation at acid pH is conserved.
ADDITIONAL INFORMATIONNo data available