title: Solid-state NMR structural studies of the fibril form of a mutant mouse prion peptide PrP89-143(P101L).
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 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.
authors.affiliation: Department of Chemistry, University of California, USA.
authors.forename: Kwang Hun
authors.initials: KH
authors.lastname: Lim
authors.forename: Tuan N
authors.initials: TN
authors.lastname: Nguyen
authors.forename: Steven M
authors.initials: SM
authors.lastname: Damo
authors.forename: Tanya
authors.initials: T
authors.lastname: Mazur
authors.forename: Haydn L
authors.initials: HL
authors.lastname: Ball
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: Alexander
authors.initials: A
authors.lastname: Pines
authors.forename: David E
authors.initials: DE
authors.lastname: Wemmer
mesh_terms: D000682:Amyloid / Q000032:analysis* / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D002247:Carbon Isotopes; D003461:Crystallography / Q000379:methods*; D051379:Mice; D046912:Multiprotein Complexes / Q000032:analysis / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011328:Prions / Q000032:analysis* / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation
chemical_list: D000682:Amyloid; D002247:Carbon Isotopes; D046912:Multiprotein Complexes; D011328:Prions