TY - JOUR
T1 - Solid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration
AU - Laws, David D.
AU - Bitter, Hans Marcus L
AU - Liu, Kai
AU - Ball, Haydn L.
AU - Kaneko, Kiyatoshi
AU - Wille, Holger
AU - Cohen, Fred E.
AU - Prusiner, Stanley B.
AU - Pines, Alexander
AU - Wemmer, David E.
PY - 2001/9/25
Y1 - 2001/9/25
N2 - 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 13C 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 13C chemical shifts, we have determined that both wild-type and mutant sequence MoPrP(89-143) form a mixture of β-sheet and α-helical conformations in the randomly aggregated state although the β-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 β-sheet, suggesting that the formation of a specific β-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.
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 13C 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 13C chemical shifts, we have determined that both wild-type and mutant sequence MoPrP(89-143) form a mixture of β-sheet and α-helical conformations in the randomly aggregated state although the β-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 β-sheet, suggesting that the formation of a specific β-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.
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U2 - 10.1073/pnas.201404298
DO - 10.1073/pnas.201404298
M3 - Article
C2 - 11562491
AN - SCOPUS:0035949709
SN - 0027-8424
VL - 98
SP - 11686
EP - 11690
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
ER -