In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 20 ( 2001-09-25), p. 11686-11690
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 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 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.201404298
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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