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

Lim KH, Nguyen TN, Damo SM, Mazur T, Ball HL, Prusiner SB, Pines A, Wemmer DE

Department of Chemistry, University of California, USA.

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 PrP(89-143)(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 (13)C=O 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.

Published 19 December 2005 in Solid State Nucl Magn Reson, 29(1): 183-90.
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