Dictionary of Human Evolution and Biology

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Prion Conversion Mechanism

In humans, the modification of the native cellular prion protein (PrPc) to the infectious form appears to require two events:

1. a genotypic predisposition to conversion (see methionine homozygosity);

2. exposure to the infectious form of the prion protein (PrPSc) derived ultimately from sheep (but infected beef can be an intermediate vector). In addition to the requirement of MM (or VV) homozygosity at codon 129, a second mutation in native PrPc at codon 178 (aspartic acid to asparagine) is also required. The normal 3D topology is somehow disturbed by this second mutation, causing templated refolding, and the final result is PrPSc, a mutant isoform of PrPc. A second prion-like particle (see Doppel protein), also seems to participate in this process. It is assumed that the conversion process cascades in brain tissue, producing symptomatic ameloid-filled spongiform abscesses and progressive muscular and cognitive impairment.

See transmissible spongiform encephalopathies and defective ribosomal products.

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