NR AHBZ
AU Laws,D.D.; Bitter,H.M.; Liu,K.; Ball,H.L.; Kaneko,K.; Wille,H.; Cohen,F.E.; Prusiner,S.B.; Pines,A.; Wemmer,D.E.
TI Solid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration
QU Proceedings of the National Academy of Sciences of the United States of America 2001 Sep 25; 98(20): 11686-90
PT journal article
AB The secondary structure of a 55-residue fragment of the mouse prion protein, MoPrP(89-143), was studied in randomly aggregated (dried from water) and fibrillar (precipitated from water/acetonitrile) forms by (13)C solid-state NMR. Recent studies have shown that the fibrillar form of the P101L mutant of MoPrP(89-143) is capable of inducing prion disease in transgenic mice, whereas unaggregated or randomly aggregated samples do not provoke disease. Through analysis of (13)C chemical shifts, we have determined that both wild-type and mutant sequence MoPrP(89-143) form a mixture of beta-sheet and alpha-helical conformations in the randomly aggregated state although the beta-sheet content in MoPrP(89-143, P101L) is significantly higher than in the wild-type peptide. In a fibrillar state, MoPrP(89-143, P101L) is completely converted into beta-sheet, suggesting that the formation of a specific beta-sheet structure may be required for the peptide to induce disease. Studies of an analogous peptide from Syrian hamster PrP verify that sequence alterations in residues 101-117 affect the conformation of aggregated forms of the peptides.
MH Amino Acid Sequence; Amino Acid Substitution; Animal; Carbon Isotopes; Isotope Labeling/methods; Mice; Mice, Transgenic; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular/methods; Peptide Fragments/*chemistry; Phosphoprotein Phosphatase/*chemistry; Prion Diseases; Prions/*chemistry; Protein Conformation; Protein Structure, Secondary; Sequence Alignment; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.
AD David D. Laws, Hans-Marcus L. Bitter, Kai Liu, Alexander Pines, David E. Wemmer (dewemmer@LBL.gov), Department of Chemistry, University of California, Berkeley, CA 94720; David D. Laws, Hans-Marcus L. Bitter, Alexander Pines, Materials Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720; Kai Liu, David E. Wemmer, Physical Biosciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720; Haydn L. Ball, Kiyatoshi Kaneko, Holger Wille, Stanley B. Prusiner, Department of Neurology, University of California, San Francisco, CA 94143; Fred E. Cohen, Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA
SP englisch
PO USA