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Updated: Apr 7, 2026

Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast
Published on: June 23, 2018
Mediator tail subunits can form amyloid-like aggregates in vivo and affect stress response in yeast
Xuefeng Zhu1, Lihua Chen2, Jonas O P Carlsten1
1Institute of Biomedicine, University of Gothenburg, P.O. Box 440, SE-405 30 Göteborg, Sweden.
Abstract:
The Med2, Med3 and Med15 proteins form a heterotrimeric subdomain in the budding yeast Mediator complex. This Med15 module is an important target for many gene specific transcription activators. A previous proteome wide screen in yeast identified Med3 as a protein with priogenic potential. In the present work, we have extended this observation and demonstrate that both Med3 and Med15 form amyloid-like protein aggregates under H2O2 stress conditions. Amyloid formation can also be stimulated by overexpression of Med3 or of a glutamine-rich domain present in Med15, which in turn leads to loss of the entire Med15 module from Mediator and a change in stress response. In combination with genome wide transcription analysis, our data demonstrate that amyloid formation can change the subunit composition of Mediator and thereby influence transcriptional output in budding yeast.
Insights
Budding yeast Med3 and Med15 proteins form amyloid aggregates under stress, impacting Mediator complex composition and altering stress response gene expression.
Area of Science:
- Molecular Biology
- Yeast Genetics
- Protein Aggregation
Background:
- The Mediator complex is crucial for gene transcription regulation in yeast.
- Med2, Med3, and Med15 proteins form a key heterotrimeric module within the Mediator complex.
- Med15 is a known target for transcription activators, and Med3 was previously identified as having aggregation potential.
Purpose of the Study:
- To investigate the aggregation behavior of Med3 and Med15 proteins under stress conditions.
- To determine the consequences of Med3 and Med15 aggregation on Mediator complex integrity and function.
- To explore the impact of altered Mediator composition on yeast stress response.
Main Methods:
- Induction of protein aggregation using hydrogen peroxide (H2O2) stress.
- Overexpression of Med3 and a glutamine-rich domain of Med15.
- Analysis of Mediator complex subunit composition.
- Genome-wide transcription analysis to assess stress response changes.
Main Results:
- Med3 and Med15 proteins form amyloid-like aggregates under H2O2 stress.
- Overexpression of Med3 or Med15's glutamine-rich domain promotes aggregation.
- Amyloid formation leads to the dissociation of the Med15 module from the Mediator complex.
- Changes in Mediator subunit composition result in altered stress response gene expression.
Conclusions:
- Amyloid formation of Med3 and Med15 is a stress-induced phenomenon in budding yeast.
- Mediator complex subunit composition can be dynamically altered by protein aggregation.
- This alteration in Mediator structure influences the transcriptional output and stress adaptation of yeast cells.
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