Computational Studies of the Structural Stability of Rabbit Prion Protein Compared to Human and Mouse Prion Proteins

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. The neurodegenerative diseases such as Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob diseases, Gerstmann-Sträussler-Scheinker syndrome, Fatal Familial Insomnia, Kuru in humans, scrapie in sheep, bovine spongiform encephalopathy (or ‘mad-cow’ disease) and chronic wasting disease in cattle belong to prion diseases. By now there have not been some effective therapeutic approaches to treat all these prion diseases. In 2008, canine mammals including dogs (canis familials) were the first time academically reported to be resistant to prion diseases Polymenidoua et al. (2008). Rabbits are the mammalian species known to be resistant to infection from prion diseases from other species Vorberg et al. (2003). Horses were reported to be resistant to prion diseases too Perez et al. (2010). By now all the NMR structures of dog, rabbit and horse prion proteins had been released into protein data bank respectively in 2005, 2007 and 2010 Lysek et al. (2005); Perez et al. (2010); Wen et al. (2010a). Thus, at this moment it is very worth studying the NMRmolecular structures of horse, dog and rabbit prion proteins to obtain insights into their immunity prion diseases. The author found that dog and horse prion proteins have stable molecular dynamical structures whether under neutral or low pH environments, but rabbit prion protein has stable molecular dynamical structures only under neutral pH environment. Under low pH environment, the stable α-helical molecular structures of rabbit prion protein collapse into β-sheet structures. This article focuses the studies on rabbit prion protein (within its C-terminal NMR, X-ray and Homology molecular structured region RaPrPC (120-230)), compared with human and mouse prion proteins (HuPrPC (125-228) and MoPrPC (124-226) respectively). The author finds that some salt bridges contribute to the structural stability of rabbit prion protein under neutral pH environment. As we all know, the disease infectious prions PrPSc are rich in β-sheets (about 43% β-sheet) Griffith (1967) and the normal cellular prions PrPC are predominant in α-helices (42% α-helix, 3% β-sheet) Pan et al. (1993). Prion diseases are believed caused by the conversion of 14