NR AJAD
AU Okimoto,N.; Yamanaka,K.; Suenaga,A.; Hata,M.; Hoshino,T.
TI Computational studies on prion proteins: effect of Ala(117) -> Val mutation.
QU Biophysical Journal 2002 May; 82(5): 2746-57
PT journal article
AB Molecular dynamics calculations demonstrated the conformational change in the prion protein due to Ala(117) ->Val mutation, which is related to Gerstmann-Sträussler-Sheinker disease, one of the familial prion diseases. Three kinds of model structures of human and mouse prion proteins were examined: (model 1) nuclear magnetic resonance structures of human prion protein HuPrP (125-228) and mouse prion protein MoPrP (124-224), each having a globular domain consisting of three alpha-helices and an antiparallel beta-sheet; (model 2) extra peptides including Ala(117) (109-124 in HuPrP and 109-123 in MoPrP) plus the nuclear magnetic resonance structures of model 1; and (model 3) extra peptides including Val(117) (109-124 in HuPrP and 109-123 in MoPrP) plus the nuclear magnetic resonance structures of model 1. The results of molecular dynamics calculations indicated that the globular domains of models 1 and 2 were stable and that the extra peptide in model 2 tended to form a new alpha-helix. On the other hand, the globular domain of model 3 was unstable, and the beta-sheet region increased especially in HuPrP.
MH *Alanine; Amino Acid Sequence; Amino Acid Substitution; Computer Simulation; Electrostatics; Gerstmann-Sträussler-Scheinker Disease/genetics; Human; Magnetic Resonance Spectroscopy; Mathematics; Models, Molecular; Models, Theoretical; Molecular Sequence Data; Mutagenesis, Site-Directed; Prions/*chemistry/genetics; Protein Conformation; Protein Structure, Secondary; Support, Non-U.S. Gov't; *Valine
AD Advanced Computing Center, Computational Science Division, Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. okimoto@atlas.riken.go.jp
SP englisch
PO USA