The N-terminus of the prion protein is a toxic effector regulated by the C-terminus.

ABSTRACT: PrP^C, the cellular isoform of the prion protein, serves to transduce the neurotoxic effects of PrP^Sc, the infectious isoform, but how this occurs is mysterious. Here, using a combination of electrophysiological, cellular, and biophysical techniques, we show that the flexible, N-terminal domain of PrP^C functions as a powerful toxicity-transducing effector whose activity is tightly regulated in cis by the globular C-terminal domain. Ligands binding to the N-terminal domain abolish the spontaneous ionic currents associated with neurotoxic mutants of PrP, and the isolated N-terminal domain induces currents when expressed in the absence of the C-terminal domain. Anti-PrP antibodies targeting epitopes in the C-terminal domain induce currents, and cause deg

SUBMITTER: Wu B 

PROVIDER: S-EPMC5469617 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature