Strain-specific morphologies of yeast prion amyloid fibrils
Abstract
Mass per length (mpl) measurements on single amyloid fibrils that specifically propagate the [VH], [VK], and [VL] strains of the yeast prion [PSI] reveal unanticipated differences in their structures. Many fibrils have ≈1.0 prion molecule per 4.7-Å cross-β repeat period, which is consistent with a self-replicating model built by parallel β-sheet hydrogen-bonding of like prion peptide segments, but other fibrils are definitely heavier. The predominantly straight fibrils of the dominant [VH] strain have a bimodal mpl distribution, corresponding to components with ≈1.0 and 1.2 prions per repeat. Fibrils of the weaker [VK] strain, which are almost all wavy, have a monodisperse mpl distribution with a mean of 1.15 prions per repeat. The recessive [VL] strain sample has ≈1.05 prions per repeat in single fibrils and includes ≈10% double fibrils, which are rare in the duplicate [VH] and [VK] samples. All of these samples were assembled from purified recombinant Sup35 prion protein by seeded growth on nuclei extracted from yeast bearing the three [PSI] strains. Infectious and noninfectious spontaneously assembled fibrils of the recombinant prion protein also display different heterogeneous morphologies. The strain-specific morphological differences we have observed directly confirm the structural prediction of the protein-only prion theory but do not have an obvious molecular explanation.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- July 2005
- DOI:
- 10.1073/pnas.0504599102
- Bibcode:
- 2005PNAS..10210165D
- Keywords:
-
- mass per length;
- scanning transmission electron microscopy;
- cross-β ply;
- [PSI] propagation;
- nucleated assembly;
- Biophysics, Biological Sciences