NR AUBK
AU Lim,K.H.; Nguyen,T.N.; Damo,S.M.; Mazur,T.; Ball,H.L.; Prusiner,S.B.; Pines,A.; Wemmer,D.E.
TI Solid-state NMR structural studies of the fibril form of a mutant mouse prion peptide PrP89-143(P101L)
QU Solid State Nuclear Magnetic Resonance 2006 Feb; 29(1-3): 183-90
PT journal article
AB 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.
MH Amyloid/*analysis/*chemistry/genetics; Animals; Carbon Isotopes; Crystallography/*methods; Mice; Multiprotein Complexes/analysis/chemistry; Mutagenesis, Site-Directed; Nuclear Magnetic Resonance, Biomolecular/*methods; Prions/*analysis/*chemistry/genetics; Protein Conformation; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
AD Department of Chemistry, University of California, USA
SP englisch
PO Niederlande