title: Computational studies on prion proteins: effect of Ala(117)-->Val mutation.
abstract: 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.
authors.affiliation: 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
authors.forename: Noriaki
authors.initials: N
authors.lastname: Okimoto
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suenaga
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hata
authors.forename: Tyuji
authors.initials: T
authors.lastname: Hoshino
mesh_terms: D000409:Alanine; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D003198:Computer Simulation; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008433:Mathematics; D008958:Models, Molecular; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011328:Prions / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D055672:Static Electricity; D014633:Valine
chemical_list: D011328:Prions; D014633:Valine; D000409:Alanine