The ?-helical C-terminal domain of full-length recombinant PrP converts to an in-regi
 

The ?-helical C-terminal domain of full-length recombinant PrP converts to an in-register parallel ?-sheet structure in PrP fibrils: Evidence from solid state NMR.

Related Articles The ?-helical C-terminal domain of full-length recombinant PrP converts to an in-register parallel ?-sheet structure in PrP fibrils: Evidence from solid state NMR.

Biochemistry. 2010 Oct 6;

Authors: Tycko R, Savtchenko R, Ostapchenko VG, Makarava N, Baskakov IV

We report the results of solid state nuclear magnetic (NMR) measurements on amyloid fibrils formed by the full-length prion protein PrP (residues 23-231, Syrian hamster sequence). Measurements of intermolecular 13C-13C dipole-dipole couplings in selectively carbonyl-labeled samples indicate that ?-sheets in these fibrils have an in-register parallel structure, as previously observed in amyloid fibrils associated with Alzheimer's disease and type 2 diabetes and in yeast prion fibrils. Two-dimensional 13C-13C and 15N-13C solid state NMR spectra of a uniformly 15N,13C-labeled sample indicate that a relatively small fraction of the full sequence, localized to the C-terminal end, forms the structurally ordered, immobilized core. Although unique site-specific assignments of the solid state NMR signals can not be obtained from these spectra, analysis with a Monte Carlo/simulated annealing algorithm suggests that the core is comprised primarily of residues in the 173-224 range. These results are consistent with earlier electron paramagnetic resonance studies of fibrils formed by residues 90-231 of the human PrP sequence, formed under somewhat different conditions [N.J. Cobb, F.D. Sonnichsen, H. McHaourab, and W.K. Surewicz (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 18946-18951], suggesting that an in-register parallel ?-sheet structure formed by the C-terminal end may be a general feature of PrP fibrils prepared in vitro.

PMID: 20925423 [PubMed - as supplied by publisher]



Source: PubMed