National Institute of Animal Health (NIAH)

Topics in Animal Health Research 2012

14. Comparison of the local structural stabilities of six mammalian prion proteins (PrPs) and their susceptibility to BSE prion infection

Japanese

Bovine spongiform encephalopathy (BSE), a member of the prion diseases, is a fatal neurodegenerative disorder that is suspected to be caused by a malfunction of prion protein (PrP). Although BSE prions have been reported to be transmitted to a wide range of animal species, dogs and hamsters are known to be BSE-resistant animals. Analysis of canine and hamster PrP could elucidate the molecular mechanisms supporting the species barriers to BSE prion transmission. The structural stability of six mammalian PrPs, including human, cattle, mouse, hamster, dog, and cat, were analysed. We then evaluated the intramolecular interactions of PrP by fragment molecular orbital (FMO) calculations. Despite similar backbone structures, the PrP side-chain orientations differed among the animal species examined. The pair interaction energies between secondary structural elements in the PrPs varied considerably, indicating that the local structural stabilities of PrP varied between the different animal species. Principal component analysis (PCA) demonstrated that different local structural stability exists in bovine PrP compared with the PrP of the other animal species examined. The results of the present study suggest that differences between canine and bovine PrP in their local structural stabilities, might be associated with the variation in susceptibility to BSE prion infection.
(Prion Disease Research Center)

References:

  • Hasegawa K. et al. (2010) Prion 4(1):38-44
  • Hasegawa K. et al. (2013) Prion 7(2):185-191

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