Prion protein and species barriers in the transmissible spongiform encephalopathies.
In the transmissible spongiform encephalopathies (TSE), the conversion of the normal protease-sensitive host protein PrP-sen to an abnormal protease-resistant form, PrP-res, is a critical step in disease pathogenesis. Amino acid mismatches between PrP-sen and PrP-res can dramatically affect the amount of PrP-res made and modulate the resistance to cross-species transmission of TSE infectivity. Experiments in transgenic mice, tissue culture cells, and cell-free systems have been used to identify the regions in PrP important in PrP-res formation. These studies have all shown that homology in the middle third of the PrP molecule is critical for the species-specific formation of PrP-res. Polymorphisms within this region correlate with the resistance of hamsters and some goats to scrapie and bovine spongiform encephalopathy (BSE) while homology at critical amino acid residues might facilitate cross-species transmission of BSE to humans. Studies such as these have proven invaluable in understanding the molecular basis of species barriers in the TSE as well as the important secondary structures involved in the formation of PrP-res.
Priola
S A
SA
Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA.
D000818:Animals; D006801:Humans; D017096:Prion Diseases / Q000378:metabolism* / Q000635:transmission; D011328:Prions / Q000378:metabolism*; D013045:Species Specificity
D011328:Prions