Intrinsic toxicity of the cellular prion protein is regulated by its conserved central region.

The conserved central region (CR) of PrP has been hypothesized to serve as a passive linker connecting the protein's toxic N-terminal and globular C-terminal domains. Yet, deletion of the CR causes neonatal fatality in mice, implying the CR possesses a protective function. The CR encompasses the regulatory α-cleavage locus, and additionally facilitates a regulatory metal ion-promoted interaction between the PrP N- and C-terminal domains.