The ribosome-associated complex antagonizes prion formation in yeast

Prion
Alvaro J AmorDale M Cameron

Abstract

The number of known fungal proteins capable of switching between alternative stable conformations is steadily increasing, suggesting that a prion-like mechanism may be broadly utilized as a means to propagate altered cellular states. To gain insight into the mechanisms by which cells regulate prion formation and toxicity we examined the role of the yeast ribosome-associated complex (RAC) in modulating both the formation of the [PSI(+)] prion - an alternative conformer of Sup35 protein - and the toxicity of aggregation-prone polypeptides. The Hsp40 RAC chaperone Zuo1 anchors the RAC to ribosomes and stimulates the ATPase activity of the Hsp70 chaperone Ssb. We found that cells lacking Zuo1 are sensitive to over-expression of some aggregation-prone proteins, including the Sup35 prion domain, suggesting that co-translational protein misfolding increases in Δzuo1 strains. Consistent with this finding, Δzuo1 cells exhibit higher frequencies of spontaneous and induced prion formation. Cells expressing mutant forms of Zuo1 lacking either a C-terminal charged region required for ribosome association, or the J-domain responsible for Ssb ATPase stimulation, exhibit similarly high frequencies of prion formation. Our findings are consisten...Continue Reading

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Citations

Mar 13, 2016·Current Genetics·Yury O Chernoff, Denis A Kiktev
Nov 10, 2016·PLoS Genetics·Kathryn M Keefer, Heather L True
Nov 7, 2016·Cold Spring Harbor Perspectives in Biology·Tatiana A ChernovaYury O Chernoff
Sep 22, 2017·Current Genetics·Andrew G MatveenkoGalina A Zhouravleva
Feb 3, 2019·The Journal of Biological Chemistry·Reed B Wickner
Apr 19, 2019·Viruses·Andrea N KillianJustin K Hines
Jul 9, 2020·International Journal of Molecular Sciences·Reed B WicknerMadaleine Niznikiewicz
Oct 7, 2020·Proceedings of the National Academy of Sciences of the United States of America·Moonil Son, Reed B Wickner
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Jul 29, 2021·Current Genetics·Reed B WicknerMadaleine Niznikiewicz
Jan 30, 2018·Biochemistry·Reed B WicknerHerman K Edskes
Oct 4, 2018·Chemical Reviews·Corey J WilsonJennifer M Heemstra

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Methods Mentioned

BETA
environmental stresses
flow cytometry
confocal microscopy
nucleotide exchange
PCR

Software Mentioned

ImageJ

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