Prion protein with a mutant N-terminal octarepeat region undergoes cobalamin-dependent assembly into high-molecular weight complexes.

ABSTRACT: The cellular prion protein (PrP^C) has a C-terminal globular domain and a disordered N-terminal region encompassing five octarepeats (ORs). Encounters between Cu(II) ions and four OR sites produce interchangeable binding geometries; however, the significance of Cu(II) binding to ORs in different combinations is unclear. To understand the impact of specific binding geometries, OR variants were designed that interact with multiple or single Cu(II) ions in specific locked coordinations. Unexpectedly, we found that one mutant produced detergent-insoluble, protease-resistant species in cells in the absence of exposure to the infectious prion protein isoform, scrapie-associated prion protein (PrP^Sc). Formation of these assemblies, visible as puncta, was reversible and depend

SUBMITTER: Daude N 

PROVIDER: S-EPMC9010764 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature