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Heterogeneous seeding of a prion structure by a generic amyloid form of the fungal prion-forming domain HET-s(218-289)

  • Author(s): Wan, W
  • Bian, W
  • McDonald, M
  • Kijac, A
  • Wemmer, DE
  • Stubbs, G
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795258/
No data is associated with this publication.
Abstract

The fungal prion-forming domain HET-s(218-289) forms infectious amyloid fibrils at physiological pH that were shown by solid-state NMR to be assemblies of a two-rung β-solenoid structure. Under acidic conditions, HET-s(218-289) has been shown to form amyloid fibrils that have very low infectivity in vivo, but structural information about these fibrils has been very limited. We show by x-ray fiber diffraction that the HET-s(218-289) fibrils formed under acidic conditions have a stacked β-sheet architecture commonly found in short amyloidogenic peptides and denatured protein aggregates. At physiological pH, stacked β-sheet fibrils nucleate the formation of the infectious β-solenoid prions in a process of heterogeneous seeding, but do so with kinetic profiles distinct from those of spontaneous or homogeneous (seeded with infectious β-solenoid fibrils) fibrillization. Several serial passages of stacked β-sheet-seeded solutions lead to fibrillization kinetics similar to homogeneously seeded solutions. Our results directly show that structural mutation can occur between substantially different amyloid architectures, lending credence to the suggestion that the processes of strain adaptation and crossing species barriers are facilitated by structural mutation. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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