The repeat domain of the functional amyloid Pmel17 forms amyloid fibrils at the acidic melanosomal pH

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NHLBI	BIOCHEM/CHEM-18

Authors

• RP McGlinchey
• JC Lee

Abstract

Most amyloids are pathological. Pmel17 is a functional amyloid, promoting melanin deposition and possibly protecting cells from adverse effects of the reactive groups that comprise this important pigment. Here, we show that at the mildly acidic pH (4 – 5.5) typical of melanosomes, organelles where melanin is synthesized, the repeat domain (RPT) of human Pmel17 can form amyloid in vitro. Combined with the known presence of RPT in the melanosomal filaments and the requirement of this domain for fibril formation, we propose that RPT may constitute the amyloid core in vivo. Upon titration to neutral pH, these fibrils dissolve, supporting a regulatory mechanism whereby if released and exposed to neutral pH outside the melanosome, would dissolve and maintain a non-toxic form. Recently, our efforts are focused on understanding at the molecular level, which residue(s) contribute to the pH dependence of RPT amyloid formation.

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