Controlling protein stability with SULI, a highly sensitive tag for stabilization upon light induction

Miaowei Mao; Yajie Qian; Wenyao Zhang; Siyu Zhou; Zefeng Wang; Xianjun Chen; Yi Yang

doi:10.1038/s41467-023-37830-0

Controlling protein stability with SULI, a highly sensitive tag for stabilization upon light induction

Nat Commun. 2023 Apr 15;14(1):2172. doi: 10.1038/s41467-023-37830-0.

Authors

Miaowei Mao^#^{1

2

3}, Yajie Qian^#^{1

2}, Wenyao Zhang^#¹, Siyu Zhou^{1

2}, Zefeng Wang³, Xianjun Chen^{4

5}, Yi Yang^{6

7}

Affiliations

¹ Optogenetics & 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.
² Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China.
³ Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
⁴ Optogenetics & 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. xianjunchen@ecust.edu.cn.
⁵ Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China. xianjunchen@ecust.edu.cn.
⁶ Optogenetics & 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. yiyang@ecust.edu.cn.
⁷ Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China. yiyang@ecust.edu.cn.

^# Contributed equally.

Abstract

Optogenetics tools for precise temporal and spatial control of protein abundance are valuable in studying diverse complex biological processes. In the present study, we engineer a monomeric tag of stabilization upon light induction (SULI) for yeast and zebrafish based on a single light-oxygen-voltage domain from Neurospora crassa. Proteins of interest fused with SULI are stable upon light illumination but are readily degraded after transfer to dark conditions. SULI shows a high dynamic range and a high tolerance to fusion at different positions of the target protein. Further studies reveal that SULI-mediated degradation occurs through a lysine ubiquitination-independent proteasome pathway. We demonstrate the usefulness of SULI in controlling the cell cycle in yeast and regulating protein stability in zebrafish, respectively. Overall, our data indicate that SULI is a simple and robust tool to quantitatively and spatiotemporally modulate protein levels for biotechnological or biomedical applications.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Fungal Proteins / chemistry
Optogenetics* / methods
Protein Domains
Protein Engineering* / methods
Protein Stability*
Saccharomyces cerevisiae
Zebrafish

Substances

Fungal Proteins