title: Evaluating prion models based on comprehensive mutation data of mouse PrP.
abstract: The structural details of the essential entity of prion disease, fibril prion protein (PrP(Sc)), are still elusive despite the large body of evidence supporting the prion hypothesis. Five major working models of PrP(Sc) structure, which are not compatible with each other, have been proposed. However, no systematic evaluation has been performed on those models. We devised a method that combined systematic point mutation with threading on knowledge-based amino acid potentials. A comprehensive mutation experiment was performed on mouse prion protein, and the PrP(Sc) conversion efficiency of each mutant was examined. The models were evaluated based on the mutation data by using the threading method. Although the data turned out to be rather more consistent with the models that assumed a conversion of the N-terminal region of core PrP into a β helix than with others, substantial modifications were also required to further improve the current model based on recent experimental results.
authors.affiliation: Department of Computer Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan; Bioinformatics Research Division, Japan Science and Technology Agency, 5-3, Yonbancho, Chiyoda-ku, Tokyo 102-8666 Japan. Electronic address: t_shirai@nagahama-i-bio.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shirai
authors.affiliation: Department of Computer Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan; Bioinformatics Research Division, Japan Science and Technology Agency, 5-3, Yonbancho, Chiyoda-ku, Tokyo 102-8666 Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine Research, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine Research, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asano
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine Research, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hizume
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine Research, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine Research, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Teruya
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine Research, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Research and Development Division, Benesis Corporation, Kitahama, Chuo-Ku, Osaka 541-850, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine Research, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Electronic address: kitamoto@med.tohoku.ac.jp.
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kitamoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D015870:Gene Expression; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017354:Point Mutation; D018620:PrPSc Proteins / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D014162:Transfection
chemical_list: D018620:PrPSc Proteins; D011994:Recombinant Proteins