Copper drives prion protein phase separation and modulates aggregation.

ABSTRACT: Prion diseases are characterized by prion protein (PrP) transmissible aggregation and neurodegeneration, which has been linked to oxidative stress. The physiological function of PrP seems related to sequestering of redox-active Cu²⁺, and Cu²⁺ dyshomeostasis is observed in prion disease brain. It is unclear whether Cu²⁺ contributes to PrP aggregation, recently shown to be mediated by PrP condensation. This study indicates that Cu²⁺ promotes PrP condensation in live cells at the cell surface and in vitro through copartitioning. Molecularly, Cu²⁺ inhibited PrP β-structure and hydrophobic residues exposure. Oxidation, induced by H₂O₂, triggered liquid-to-solid transition of PrP:Cu²⁺ condensates and promoted

SUBMITTER: do Amaral MJ 

PROVIDER: S-EPMC10624353 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature