Comparison studies of the structural stability of rabbit prion protein with human and mouse prion proteins

Prion diseases are fatal and infectious neurodegenerative diseases affecting humans and animals. Rabbits are one of the few mammalian species reported to be resistant to infection from prion diseases isolated from other species (I. Vorberg et al., Journal of Virology 77 (3) (2003) 2003-2009). Thus the study of rabbit prion protein structure to obtain insight into the immunity of rabbits to prion diseases is very important.

The paper is a straight forward molecular dynamics simulation study of wild-type rabbit prion protein (monomer cellular form) which apparently resists the formation of the scrapie form. The comparison analyses with human and mouse prion proteins done so far show that the rabbit prion protein has a stable structure. The main point is that the enhanced stability of the C-terminal ordered region especially helix 2 through the D177-R163 salt-bridge formation renders the rabbit prion protein stable. The salt bridge D201-R155 linking helixes 3 and 1 also contributes to the structural stability of rabbit prion protein. The hydrogen bond H186-R155 partially contributes to the structural stability of rabbit prion protein.

Rabbit prion protein was found to own the structural stability, the salt bridges D177-R163, D201-R155 greatly contribute and the hydrogen bond H186-R155 partially contributes to this structural stability. The comparison of the structural stability of prion proteins from the three species rabbit, human and mouse showed that the human and mouse prion protein structures were not affected by the removing these two salt bridges. Dima et al. (Biophysical Journal 83 (2002) 1268-1280 and Proceedings of the National Academy of Sciences of the United States of America 101 (2004) 15335-15340) also confirmed this point and pointed out that "correlated mutations that reduce the frustration in the second half of helix 2 in mammalian prion proteins could inhibit the formation of PrP(Sc)".