Controlling protein stability with SULI, a highly sensitive tag for stabilization upon light induction.
Miaowei Mao1,2,3, Yajie Qian1,2, Wenyao Zhang1
1Optogenetics & Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China.
Nature Communications
|April 15, 2023
Summary
Researchers developed a new optogenetic tool called Stabilization Upon Light Induction (SULI) for precisely controlling protein levels in cells. This SULI tag enables light-activated protein stability and dark-induced degradation, offering new possibilities for biological research.
Area of Science:
- Molecular Biology
- Optogenetics
- Biotechnology
Background:
- Optogenetics offers precise control over biological processes.
- Tools for modulating protein abundance are crucial for studying complex biological systems.
- Existing methods may lack sufficient temporal or spatial resolution.
Purpose of the Study:
- To engineer a novel optogenetic tool for controlling protein levels.
- To develop a monomeric tag for light-inducible protein stabilization and degradation.
- To validate the tool's efficacy in yeast and zebrafish models.
Main Methods:
- Engineering of a monomeric tag (SULI) based on a Neurospora crassa light-oxygen-voltage domain.
- Fusion of target proteins with the SULI tag.
- Light-induced protein stabilization and dark-induced degradation experiments.
- Assessment of SULI's dynamic range and fusion tolerance.
- Investigation of the degradation pathway (proteasome-mediated, lysine ubiquitination-independent).
- Demonstration in yeast cell cycle control and zebrafish protein regulation.
Main Results:
- Successful engineering of the SULI tag for yeast and zebrafish.
- SULI-tagged proteins are stable under light and degraded in the dark.
- SULI exhibits a high dynamic range and tolerance to fusion at various protein positions.
- SULI-mediated degradation proceeds via a lysine ubiquitination-independent proteasome pathway.
- Demonstrated utility in controlling yeast cell cycle and zebrafish protein stability.
Conclusions:
- SULI is a simple, robust optogenetic tool for quantitative, spatiotemporal modulation of protein levels.
- The tool has potential applications in biotechnology and biomedical research.
- SULI provides a novel method for precise control over protein abundance in living systems.
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