The potential stem-forming sequence consists of the polymerization in Pmel17

Abstract

Polymerization accelerated by Pmel17, advanced within the mildly acidic conditions of melanosomes, plays a vital role during pigment deposition. The polymers closely resemble amyloid fibrils, associated with amyloidosis. Concerning the formation of the amyloidogenic cross-β structure, the initial mechanism in the conversion to a β-structure is critically important. To explore the core regions forming a stem of the amyloid, we prepared a series of fragment peptides of the C-terminal part of the the repeat domain (RPT, residues 315–444) and examined their ability to produce amyloids. Sequence alignment of the peptides bearing the ability to form amyloid structures revealed that β-consisting of 405 VSIVVLSGTTAAQVTT 420 are the core regions responsible for initiating the formation of cross-β structures and for further ordered aggregation.