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Sup35 methionine oxidation is a trigger for de novo [PSI(+)] prion formation

Chris M Grant1

  • 1a Faculty of Life Sciences; University of Manchester ; Manchester , UK.

Prion
|August 13, 2015
PubMed

Insights

Oxidative damage to Sup35, a protein involved in yeast prion formation, can trigger the creation of infectious [PSI(+)] prions. This discovery sheds light on spontaneous prion formation in fungi and mammals.

Area of Science:

  • Molecular biology
  • Biochemistry
  • Prion biology

Background:

  • Spontaneous prion formation in fungi and mammals remains poorly understood.
  • Environmental stress and protein misfolding are linked to prion genesis.
  • Yeast [PSI(+)] prion formation is influenced by conditions causing protein misfolding.

Purpose of the Study:

  • To investigate the role of oxidative stress in the de novo formation of yeast [PSI(+)] prions.
  • To explore the molecular mechanisms by which oxidative damage triggers prion formation.
  • To draw parallels between yeast and mammalian prion formation triggers.

Main Methods:

  • Analysis of yeast mutants lacking key antioxidants.
  • Assessment of reactive oxygen species' sufficiency in promoting prion formation.
  • Examination of Sup35 protein structure and oxidative modifications.

Main Results:

  • Yeast mutants deficient in antioxidants exhibit increased de novo [PSI(+)] prion formation.
  • Endogenous reactive oxygen species are sufficient to promote prion formation.
  • Oxidative damage to Sup35 is implicated as a key trigger for [PSI(+)] prion formation.

Conclusions:

  • Direct oxidation of Sup35 can induce structural changes favoring conversion to a transmissible amyloid form.
  • Oxidative damage provides a molecular mechanism for spontaneous prion formation in yeast.
  • This mechanism may be analogous to factors triggering mammalian prion protein misfolding.
Keywords:
[PSI+]antioxidantsmethionine oxidationoxidative stressprionsyeast

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