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 (PrP(C)) into its amyloidogenic isoform (PrP(Sc)) is still matter of debate in the field of structural biology. The NMR structures of non-mammalian PrP(C) (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 PrP(C) folding, despite their low sequence identity with the mammalian prions (mPrP). The present molecular dynamics study of non-mPrP(C) 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 PrP(C) folding stability and its propensity for interactions. In addition, for the first time, a role in disfavoring the PrP(C) aggregation is suggested for a conserved beta-bulge which is stabilized by the local hydration.
De Simone
Alfonso
A
National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA, London, UK.
Dodson
Guy G
GG
Fraternali
Franca
F
Zagari
Adriana
A
D000595:Amino Acid Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D014867:Water / Q000737:chemistry*
D011328:Prions; D014867:Water