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Updated: Aug 14, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
One-dimensional model of yeast prion aggregation
K C Kunes1, D L Cox, R R P Singh
1Department of Physics, University of California, Davis, California 95616, USA.
Abstract:
Mammalian prion proteins (PrP) are of significant public health interest. Yeasts have proteins, which can undergo similar reconformation and aggregation processes to PrP, without posing a threat to the organism. These yeast "prions," such as SUP35, are simpler to experimentally study and model. Recent in vitro studies of the SUP35 protein found long aggregates, pure exponential growth of the misfolded form, and a lag time which depended weakly on the monomer concentration. To explain this data, we have extended a previous model of aggregation kinetics along with a stochastic approach. We assume reconformation only upon aggregation and include aggregate fissioning and an initial nucleation barrier. We find that for sufficiently small nucleation rates or seeding by a small number of preformed nuclei, the models achieve the requisite exponential growth, long aggregates, and a lag time which depends weakly on monomer concentration. The spread in aggregate sizes is well described by the Weibull distribution. All these properties point to the preeminent role of fissioning in the growth of misfolded proteins.
Insights
Yeast prions like SUP35, simpler models for mammalian prion proteins (PrP), exhibit exponential growth and long aggregates. Aggregate fissioning is key to their formation and explains observed lag times and size distributions.
Area of Science:
- Biochemistry
- Molecular Biology
- Biophysics
Background:
- Mammalian prion proteins (PrP) are a public health concern.
- Yeast proteins, such as SUP35, mimic PrP misfolding and aggregation but are non-pathogenic.
- Yeast prions offer a simpler system for studying protein misfolding dynamics.
Purpose of the Study:
- To model the in vitro aggregation kinetics of the yeast SUP35 protein.
- To explain observed phenomena: long aggregates, exponential growth, and weak dependence of lag time on monomer concentration.
- To elucidate the role of aggregate fissioning in prion formation.
Main Methods:
- Extended a previous aggregation kinetics model with a stochastic approach.
- Incorporated aggregate fissioning and an initial nucleation barrier.
- Analyzed in vitro experimental data for SUP35 protein aggregation.
Main Results:
- The extended model successfully reproduced exponential growth, long aggregates, and weak lag time dependence on monomer concentration.
- Low nucleation rates or seeding with preformed nuclei were critical for achieving these results.
- Aggregate size distribution was accurately described by the Weibull distribution.
Conclusions:
- Aggregate fissioning plays a crucial role in the growth of misfolded proteins, particularly yeast prions.
- The model provides a framework for understanding prion-like protein aggregation.
- Findings contribute to the study of protein misfolding diseases.
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