Cryo-EM of wild-type and mutant PMEL amyloid cores reveals structural mechanism of pigment dispersion syndrome.

ABSTRACT: PMEL amyloids serve as essential scaffolds for melanin deposition in melanosomes, playing a crucial role in pigmentation. Despite their importance, the high-resolution structure of PMEL amyloids has remained unresolved. Using cryo-electron microscopy, we determine near-atomic resolution structures of wild-type PMEL amyloid core, revealing two distinct polymorphic forms with structural features. We further investigate the pathogenic G175S mutation associated with pigment dispersion syndrome (PDS). Structural analysis reveales that G175S introduces an additional hydrogen bond, stabilizing an alternative fibril conformation. In vitro, the G175S mutant exhibits a fourfold increase in polymerization efficiency compared to the wild type. In cells, G175S expression resultes in a twofold increase

SUBMITTER: Yanagisawa H 

PROVIDER: S-EPMC12219675 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature