Intermolecular Alignment in Y145Stop Human Prion Protein Amyloid Fibrils Probed by Solid-State NMR Spectroscopy.
 

Intermolecular Alignment in Y145Stop Human Prion Protein Amyloid Fibrils Probed by Solid-State NMR Spectroscopy.

Intermolecular Alignment in Y145Stop Human Prion Protein Amyloid Fibrils Probed by Solid-State NMR Spectroscopy.

J Am Chem Soc. 2011 Aug 10;

Authors: Helmus JJ, Surewicz K, Apostol MI, Surewicz WK, Jaroniec CP

The Y145Stop mutant of human prion protein, huPrP23-144, has been linked to PrP cerebral amyloid angiopathy, an inherited amyloid disease, and also serves as a valuable in vitro model for investigating the molecular basis of amyloid strains. Prior studies of huPrP23-144 amyloid by magic-angle spinning (MAS) solid-state NMR revealed a compact ?-rich amyloid core region near the C-terminus and an unstructured N-terminal domain. Here, with the focus on understanding the higher order architecture of huPrP23-144 fibrils, we probe the intermolecular alignment of ?-strands within the amyloid core using MAS NMR techniques and fibrils formed from equimolar mixtures of 15N-labeled protein and 13C-huPrP23-144 prepared with [1,3-13C] or [2-13C]glycerol. Numerous intermolecular correlations involving backbone atoms observed in 2D 15N-13C spectra unequivocally suggest an overall parallel in-register alignment of the ?-sheet core. Additional experiments that report on intermolecular 15N-13CO and 15N-13C? dipolar couplings yield an estimated strand spacing that is within ~10% of the ~4.7-4.8 Å distances typical for parallel ?-sheets.

PMID: 21827207 [PubMed - as supplied by publisher]



Source: PubMed