Melanosomal formation of PMEL core amyloid is driven by aromatic residues.

ABSTRACT: PMEL is a pigment cell protein that forms physiological amyloid in melanosomes. Many amyloids and/or their oligomeric precursors are toxic, causing or contributing to severe, incurable diseases including Alzheimer's and prion diseases. Striking similarities in intracellular formation pathways between PMEL and various pathological amyloids including Aβ and PrP^Sc suggest PMEL is an excellent model system to study endocytic amyloid. Learning how PMEL fibrils assemble without apparent toxicity may help developing novel therapies for amyloid diseases. Here we identify the critical PMEL domain that forms the melanosomal amyloid core (CAF). An unbiased alanine-scanning screen covering the entire region combined with quantitative electron microscopy analysis of the full set of mutants u

SUBMITTER: Hee JS 

PROVIDER: S-EPMC5341037 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature