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Yeast as a tool for membrane protein production and structure determination
Antonio Carlesso1,2,3, Raquel Delgado1, Oriol Ruiz Isant1
1Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
FEMS Yeast Research
|September 29, 2022
Summary
Yeast systems like Saccharomyces cerevisiae and Pichia pastoris are effective for producing membrane proteins for structural studies. Common protein engineering strategies improve yields for these challenging biological targets.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Membrane proteins present significant challenges for functional and structural characterization.
- Reliable production of sufficient, stable protein yields is a major bottleneck in membrane protein research.
Purpose of the Study:
- To evaluate eukaryotic membrane protein production experiments supporting high-resolution structure deposition.
- To focus on common yeast host systems: Saccharomyces cerevisiae and Pichia pastoris.
Main Methods:
- Analysis of published membrane protein production experiments linked to structural data.
- Comparison of homologous and heterologous protein production in yeast.
- Investigation of protein engineering techniques used to enhance yields.
Main Results:
- 186 high-resolution structures of alpha-helical membrane proteins produced in yeast have been deposited since 1999.
- Saccharomyces cerevisiae shows equal use of homologous and heterologous production, while Pichia pastoris favors heterologous production, particularly for human proteins.
- Protein engineering approaches, including polyhistidine tags, codon optimization, and truncation, were frequently employed.
Conclusions:
- Yeast continues to be a valuable host system for the production of alpha-helical membrane proteins for structural studies.
- Protein engineering strategies are crucial for overcoming production challenges and achieving high yields.
