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Sant'Anna R, Fernández MR, Batlle C, et al. Characterization of Amyloid Cores in Prion Domains. Sci Rep. 2016;6:34274doi: 10.1038/srep34274.
Sant'Anna, R., Fernández, M. R., Batlle, C., Navarro, S., de Groot, N. S., Serpell, L., & Ventura, S. (2016). Characterization of Amyloid Cores in Prion Domains. Scientific reports, 634274. https://doi.org/10.1038/srep34274
Sant'Anna, Ricardo, et al. "Characterization of Amyloid Cores in Prion Domains." Scientific reports vol. 6 (2016): 34274. doi: https://doi.org/10.1038/srep34274
Sant'Anna R, Fernández MR, Batlle C, Navarro S, de Groot NS, Serpell L, Ventura S. Characterization of Amyloid Cores in Prion Domains. Sci Rep. 2016 Sep 30;6:34274. doi: 10.1038/srep34274. PMID: 27686217; PMCID: PMC5043269.
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Sci Rep. 2016 Sep 30;6:34274. doi: 10.1038/srep34274.

Characterization of Amyloid Cores in Prion Domains.

Scientific reports

Ricardo Sant'Anna, Maria Rosario Fernández, Cristina Batlle, Susanna Navarro, Natalia S de Groot, Louise Serpell, Salvador Ventura

Affiliations

  1. Institut de Biotecnologia i Biomedicina and Departament de Bioquimica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
  2. School of Life Sciences, University of Sussex, Falmer, BN1 9QG, UK.

PMID: 27686217 PMCID: PMC5043269 DOI: 10.1038/srep34274

Abstract

Amyloids consist of repetitions of a specific polypeptide chain in a regular cross-β-sheet conformation. Amyloid propensity is largely determined by the protein sequence, the aggregation process being nucleated by specific and short segments. Prions are special amyloids that become self-perpetuating after aggregation. Prions are responsible for neuropathology in mammals, but they can also be functional, as in yeast prions. The conversion of these last proteins to the prion state is driven by prion forming domains (PFDs), which are generally large, intrinsically disordered, enriched in glutamines/asparagines and depleted in hydrophobic residues. The self-assembly of PFDs has been thought to rely mostly on their particular amino acid composition, rather than on their sequence. Instead, we have recently proposed that specific amyloid-prone sequences within PFDs might be key to their prion behaviour. Here, we demonstrate experimentally the existence of these amyloid stretches inside the PFDs of the canonical Sup35, Swi1, Mot3 and Ure2 prions. These sequences self-assemble efficiently into highly ordered amyloid fibrils, that are functionally competent, being able to promote the PFD amyloid conversion in vitro and in vivo. Computational analyses indicate that these kind of amyloid stretches may act as typical nucleating signals in a number of different prion domains.

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