Water molecules as structural determinants among prions of low sequence identity

The nature of the factors leading to the conversion of the cellular prion protein (PrPC) into its amyloidogenic isoform (PrPSc) is still matter of debate in the field of structural biology. The NMR structures of non-mammalian PrPC (non-mPrP) from frog, chicken and turtle [Calzolai, L., Lysek, D.A., Perez, D.R., Guntert, P. and Wuthrich, K. (2005) Prion protein NMR structures of chickens, turtles, and frogs. Proc. Natl. Acad. Sci. USA 102, 651–655] have provided some new and valuable information on the scaffolding elements that preserve the PrPC folding, despite their low sequence identity with the mammalian prions (mPrP). The present molecular dynamics study of non-mPrPC focuses on the hydration properties of these proteins in comparison with the mammalian ones. The data reveal new insights in the PrP hydration and focus on the implications for PrPC folding stability and its propensity for interactions. In addition, for the first time, a role in disfavoring the PrPC aggregation is suggested for a conserved β-bulge which is stabilized by the local hydration.