Bovine prions

There has been great concern over the large-scale outbreak of BSE that occurred in the UK from 1988 as a result of feeding cattle with supplements prepared fiom sheep and cattle offal. Brain extracts firm BSE cattle have transmitted the disease to mice, sheep, cattle, pigs and monkeys. Studies of 12 recent cases of atypical CJD in the UK have provided evidence that the bovine prions have infected humans through the consumption of contaminated beef... 

Lopez Garcia, F., Zahn, R., Riek, R., and Wiithrich, K. (2000). NMR structure of the bovine prion protein. Proc. Natl. Acad. Sci. USA 97, 8334-8339. 

ESiverstahl, H., A. Andersson, A. Graslund and L. Maler (2004) NMR solution structure and membrane interaction of the N-terminal sequence (1-30) of the bovine prion protein. Biochemistry 43, 14940-14947. 

Homemann S, Schom C, Wuthrich K (2004) NMR structure of the bovine prion protein isolated from healthy calf brains. EMBO Rep 5 1159-1164... 

Beringue V, Andreoletti O, Le Dur A, Essalmani R, Vilotte JL, Lacroux C, Reine F, Herzog L, Biacabe AG, Baron T, Caramelli M, Casalone C, Laude H (2007) A bovine prion acquires an epidemic bovine spongiform encephalopathy strain-like phenotype on interspecies transmission. J Neurosci 27 6965-6971... 

Beringue V, Herzog L, Reine F, Le Dur A, Casalone C, Vilotte JL, Laude H (2008) Transmission of atypical bovine prions to mice transgenic for human prion protein. Emerg Infect Dis 14 1898-1901... 

Julien O, Chatterjee S, Thiessen A et al (2009) Differential stability of the bovine prion protein upon urea unfolding. Protein Sci 18 2172-2182... 

Fig. 8. Cartoons of three-dimensional PrP structures. (A) Intact recombinant bovine prion protein, bPrP(23-230). (B) Intact recombinant human prion protein, hPrP(23-230). (C) Recombinant Syrian hamster prion protein, shPrP(29-231). The helices are colored green in (A), red in (B) and pink in (C) in all three structures the P strands are cyan, the segments with nonregular secondary structure within the globular domain are yellow, and the residues 23-120 in (A) and (B), and 29-124 in (C) of the flexibly disordered tail are schematically represented by yellow dots.

Although it is to be anticipated that other cellular cofactors will affect the efficiency of prion propagation, there remains no direct evidence for the existence of protein X. It is possible that the transgenetic observations that led to this hypothesis could be explained by mouse PrP itself acting to interfere with interactions between human PrP = and human PrP. Of interest, mice expressing a chimeric mouse/bovine PrP, which would be expected according to the protein X hypothesis to be more sensitive to bovine prions than mice expressing wild-type bovine PrP in the presence of mouse PrP, are in fact much less susceptible (see later). 

Pimenova, T., Nazabtil, A., Roschitzki, B., et al. (2008) Epitope Mapping on Bovine Prion Protein Using Chemical Cross-Linking and Mass Spectrometry. Journal of Mass Spectrometry, 43 (2), 185-195. 

Yin SM, Zheng Y, Tien P. On-column purification and refolding of recombinant bovine prion protein using its octarepeat sequences as a natural affinity tag. Prot Express Purif 2003 32 104-9. 

Figure 15.3. Sandwich immunocomplex analyzed by high-mass MALDI mass spectrometry A complex formed by two monoclonal antibodies (6H4 and 3B8) against the bovine prion protein (bPrP) has been cross-linked and analyzed by high-mass MALDI TOP mass spectrometry. The specific protein complex [6H4 bPrP bPrP-3B8] is...

---