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Characterization of amyloid cores in prion domains

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posted on 2023-06-09, 05:37 authored by Ricardo Sant’Anna, Maria Rosario Fernández, Cristina Batlle, Susanna Navarro, Natalia S de Groot, Louise SerpellLouise Serpell, Salvador Ventura
Amyloids consist of repetitions of a specific polypeptide chain in a regular cross-ß-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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Scientific Reports

ISSN

2045-2322

Publisher

Nature Publishing Group

Volume

6

Article number

a34274

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Dementia Research Group Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2017-04-04

First Open Access (FOA) Date

2017-04-04

First Compliant Deposit (FCD) Date

2017-04-04

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