Structure, Function and Stability of the BSE Prion

Brief background

This section is based on the author’s personal experience and knowledge of the development of BSE saga from the identification of the first BSE case at the Central Veterinary Laboratory (CVL), Weybridge, UK where the author w as Head of Toxicology at that time ) to the first cases of new variant Creutzfeldt Jakob Disease (nvCJD) in humans several years later. Dr Ray Bradley was Head of Pathology at CVL and was intimately involved in the elucidation of BSE and its cause: for his detailed ac count of the development of the disease see Bradley (1997).

Origins of the BS E prion

There is much conjecture about what initiated the BSE epidemic; but at a basic molecular biology level, this must have involved some change in the structure of PrP C that supported (thermodynamically) the spontaneous conformational change to PrP Sc. Various theories for this have been expounded ranging from cattle’s exposure to organophosphorus pesticides (Purdey, 1994) to mutations in the prion gene leading to prion misfolding (Hwang & Nicholson, 2018). The latter is the most convincing explanation because it relies on a single amino acid mutation (glutamic acid to lysine) in the gene product which introduces instability into the PrP C α helix.