Solid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration

TitleSolid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration
Publication TypeJournal Article
Year of Publication2001
AuthorsLaws D.D, Bitter H.ML, Liu K., Ball H.L, Kaneko K., Wille H., Cohen F.E, Prusiner S.B, Pines A, Wemmer D.E
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue20
Pagination11686-11690
Date PublishedSep 25
ISBN Number0027-8424
Accession NumberWOS:000171237100125
Keywordsdiseases
Abstract

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 C-13 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 C-13 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.

URL<Go to ISI>://WOS:000171237100125
DOI10.1073/Pnas.201404298
Short TitleSolid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration
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