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Updated: Oct 13, 2025
11:04
Evaluation of the Impact of Protein Aggregation on Cellular Oxidative Stress in Yeast
Published on: June 23, 2018
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Yeast Proteins may Reversibly Aggregate like Amphiphilic Molecules
Pouria Dasmeh1, Andreas Wagner2
1Institute for Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02139, USA; Swiss Institute of Bioinformatics (SIB), Switzerland.
Journal of Molecular Biology
|November 14, 2021
Summary
Yeast proteins reversibly aggregate due to sequence-encoded features, not just disorder. Aggregation-prone regions (APRs) in these proteins are enriched in aliphatic residues and contribute to phase separation alongside structured regions.
Area of Science:
- Biochemistry
- Proteomics
- Biophysics
Background:
- Over a hundred yeast proteins reversibly aggregate and phase-separate under stress.
- The sequence and structural features driving this proteome-wide phenomenon are poorly understood.
Purpose of the Study:
- To identify distinctive features of aggregation-prone protein regions (APRs).
- To investigate the role of disordered versus structured regions in protein aggregation and phase separation.
Main Methods:
- Applied machine learning algorithms to genome-scale limited proteolysis-mass spectrometry (LiP-MS) data from yeast proteins.
- Analyzed structural changes in 96 proteins exhibiting significant structural changes upon heat shock.
Main Results:
- Aggregation-prone regions (APRs) are not significantly disordered, indicating phase separation involves both disordered and structured regions.
- APRs are enriched in aliphatic residues and depleted in positively charged amino acids.
- Longer APRs correlate with increased aggregation propensity, explained by statistical thermodynamics.
Conclusions:
- Proteome-wide reversible protein aggregation is mediated by sequence-encoded properties.
- Aggregating proteins function like supra-molecular amphiphiles, with APRs acting as hydrophobic components and non-APRs as hydrophilic components.
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