Prion protein isoform interactions

Horiuchi, M., Baron, G. S., Xiong, L. W., and Caughey, B. (2001). Inhibition of interactions and interconversions of prion protein isoforms by peptide fragments from the C-terminal folded domain./. Biol. Chem. 276, 15489-15497. 

Caughey B (2001) Interactions between prion protein isoforms the kiss of death Trends Biochem Sci 26 235-242... 

Prions—protein particles that lack nucleic acid— cause fatal transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, scrapie, and bovine spongiform encephalopathy. Prion diseases involve an altered secondary-tertiary strucmre of a namrally occurring protein, PrPc. When PrPc interacts with its pathologic isoform PrPSc, its conformation is transformed from a predominantly a-helical strucmre to the P-sheet strucmre characteristic of PrPSc. 

According to the protein-only hypothesis, proposed by Prusiner (Fig. 5), the interaction of the cellular prion protein with the pathological isoform seems to be the crucial step in the conversion of PrP = to PrP . The existence of the hypothetical PrP =/PrP heterodimer may require the presence of a homodimer consisting of two PrP = molecules. This homodimer is thought to be in equilibrium with the PrP monomers. It is unclear to date wether the spontaneous conversion reaction involves PrP monomers or the PrP homodimers. 

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