The repeat domain of the melanosome fibril protein Pmel17 forms the amyloid core promoting melanin synthesis

• DOI: 10.1073/pnas.0906509106
• Publication Date: 2009-08-01T01:31:49Z
• Authors: Ryan P. McGlinchey; Frank Shewmaker; Peter McPhie; Begoña Monterroso; Kent Thurber; Reed B. Wickner
• Keywords: Melanosome; Amyloid (mycology)

Pmel17 is a melanocyte protein necessary for eumelanin deposition 1 in mammals and found melanosomes filamentous form. The luminal part of human includes region (RPT) with 10 copies partial repeat sequence, pt.e.gttp.qv., known to be essential vivo filament formation. We show that this RPT readily forms amyloid vitro, but only under the mildly acidic conditions typical lysosome-like melanosome lumen, filaments quickly become soluble at neutral pH. Under same conditions, Pmel promote Electron diffraction, circular dichroism, solid-state NMR studies structure rich beta sheet. suggest core domain so critical melanin