Solid-state NMR structural studies of the fibril form of a mutant mouse prion peptide PrP89-143(P101L)

TitleSolid-state NMR structural studies of the fibril form of a mutant mouse prion peptide PrP89-143(P101L)
Publication TypeJournal Article
Year of Publication2006
AuthorsLim K.H, Nguyen T.N, Damo S.M, Mazur T., Ball H.L, Prusiner S.B, Pines A, Wemmer D.E
JournalSolid State Nuclear Magnetic Resonance
Volume29
Issue1-3
Pagination183-190
Date PublishedFeb
ISBN Number0926-2040
Accession NumberWOS:000234417500020
Keywordsidentification
Abstract

The peptide fragment 89-143 of the prion protein (carrying a P101L mutation) is biologically active in transgenic mice when in a fibrillar form. Injection of these fibrils into transgenic mice (expressing full length PrP with the P101L mutation) induces a neurodegenerative prion disease (Kaneko et al., J. Mol. Biol. 295 (2000) 997). Here we present solid-state NMR studies of PrP89-143(P101L) fibrils, probing the conformation of residues in the hydrophobic segment 112-124 with chemical shifts. The conformations of glycine residues were analyzed using doubly C-13 = 0 labeled peptides by two-dimensional (2D) double-quantum correlation, and double-quantum filtered dephasing distance measurements. MQ-NMR experiments were carried out to probe the relative alignment of the individual peptides fibrils. These NMR studies indicate that the 112-124 segment adopts an extended beta-sheet conformation, though not in a parallel, in register alignment. There is evidence for conformational variability at Gly 113. DQ correlation experiments provide useful information in regions with conformational heterogeneity. (c) 2005 Elsevier Inc. All rights reserved.

URL<Go to ISI>://WOS:000234417500020
DOI10.1016/J.Ssnmr.2005.09.017
Short TitleSolid-state NMR structural studies of the fibril form of a mutant mouse prion peptide PrP89-143(P101L)
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