Effects of Pulsed Electric Fields on Yeast with Prions and the Structure of Amyloid Fibrils

Justina Jurgelevičiūtė,Andrius Sakalauskas,Vitalij Novickij,Eglė Lastauskienė,Vytautas Smirnovas,Nedas Bičkovas

doi:10.3390/app11062684

Justina Jurgelevičiūtė, Andrius Sakalauskas + Show 4 more

Open Access

https://doi.org/10.3390/app11062684

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Abstract

Prions are misfolded, self-replicating, and transmissible proteins capable of causing different conditions that affect the brain and nervous system in humans and animals. Yeasts are the perfect model to study prion formation, dissemination, and the structure of protein aggregates. Yeast prions are related to stress resistance, cell fitness, and viability. Applying a pulsed electric field (PEF) as a factor capable of disintegrating the amyloid aggregates arises from the fact that the amyloid aggregates form via noncovalent bonds and stabilize via electrostatic interactions. In this research, we applied 2–26 kV/cm PEF delivered in sequences of 5 pulses of 1 ms duration to the Saccharomyces cerevisiae cell without prions and containing strong and weak variants of the [PSI+] prion (prion form of Sup35 translation termination factor). We determined that prions significantly increase cell survivability and resistance to PEF treatment. The application of PEF to the purified Sup35NM fibrils showed that the electric field causes significant reductions in the length of fibrils and the full disintegration of fibrils to Sup35 oligomers can be achieved in higher fields.

Highlights

Prions are misfolded, self-replicating, and transmissible proteins that are related to the loss of function of the native protein
Applying a pulsed electric field (PEF) as a factor capable of disintegrating the amyloid aggregates arises from the fact that the amyloid aggregates form via noncovalent bonds and stabilize via electrostatic interactions
We applied 2–26 kV/cm PEF delivered in sequences of 5 pulses of 1 ms duration to the Saccharomyces cerevisiae cell without prions and containing strong and weak variants of the [PSI+] prion

Summary

Introduction

Self-replicating, and transmissible proteins that are related to the loss of function of the native protein. Yeast prions have become important research objects in elucidating the underlying mechanisms of human amyloid disease [2]. A single prion protein sequence may have several different prion variants, have a parallel β-fold amyloid structure, are harmful to their hosts by causing them stress, and are the subject of prion disease research [4,5]. Variants of [PSI+] yeast prion (an amyloid form of Sup translation termination factor) capable to manifest themselves as strong and weak forms that can be discriminated by their phenotypic intensity and stability during cell division [6]. In SUP35 protein, the Sup35NM domain, located at 1–253 residues of the amino acid sequence, is capable of inducing and propagating the prion state of the [PSI+]

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