Secondary nucleation overcomes seeding template in amyloid-like fibril formation
- Published
- Accepted
- Subject Areas
- Biochemistry, Biophysics
- Keywords
- amyloid, prion, protein misfolding, protein aggregation, amyloid-like fibrils, prion strain
- Copyright
- © 2015 Milto et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
- Cite this article
- 2015. Secondary nucleation overcomes seeding template in amyloid-like fibril formation. PeerJ PrePrints 3:e1101v1 https://doi.org/10.7287/peerj.preprints.1101v1
Abstract
Prions are infectious proteins where the same protein may express distinct strains. The strains are enciphered by different misfolded conformations. Strain-like phenomena have also been reported in a number of other amyloid-forming proteins. One of the features of amyloid strains is the ability to self-propagate, maintaining a constant set of physical properties despite being propagated under conditions different from those that allowed initial formation of the strain. Here we report a cross-seeding experiment using strains formed under different conditions. Using high concentrations of seeds results in rapid elongation and new fibrils preserve the properties of the seeding fibrils. At low seed concentrations secondary nucleation plays the major role and new fibrils gain properties predicted by the environment rather than the structure of the seeds. Our findings could explain conformational switching between amyloid strains observed in a wide variety of in vivo and in vitro experiments.
Author Comment
This is a submission to PeerJ for review.