Prion Protein Octarepeat Domain Forms Transient β-Sheet Structures upon Residue-Specific Binding to Cu(II) and Zn(II) Ions.

ABSTRACT: Misfolding of the cellular prion protein (PrP^C) is associated with the development of fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSEs). Metal ions appear to play a crucial role in PrP^C misfolding. PrP^C is a combined Cu(II) and Zn(II) metal-binding protein, where the main metal-binding site is located in the octarepeat (OR) region. Thus, the biological function of PrP^C may involve the transport of divalent metal ions across membranes or buffering concentrations of divalent metal ions in the synaptic cleft. Recent studies have shown that an excess of Cu(II) ions can result in PrP^C instability, oligomerization, and/or neuroinflammation. Here, we have used biophysical methods to characterize Cu(II) a

SUBMITTER: Gielnik M 

PROVIDER: S-EPMC10249355 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature