Red Light-Activated Reversible Inhibition of Protein Functions by Assembled Trap.
Peng Zhou1,2,3, Yongkang Jia4, Tianyu Zhang2,3
1Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
ACS Synthetic Biology
|April 30, 2025
Summary
Researchers developed a new red-light optogenetic tool, R-LARIAT, for reversible protein inhibition. This system uses light-induced protein clustering for precise control over biological processes.
Area of Science:
- Optogenetics
- Molecular Biology
- Cell Biology
Background:
- Red light is ideal for optogenetics due to deep tissue penetration and low phototoxicity.
- Existing red-light tools for reversible protein inhibition are limited.
- Need for precise spatiotemporal control of protein function in biological systems.
Purpose of the Study:
- Introduce R-LARIAT (red light-activated reversible inhibition by assembled trap), a novel optogenetic system.
- Enable precise spatiotemporal control of protein function using red light.
- Develop a tool for reversible protein clustering and inhibition.
Main Methods:
- Engineered light-dependent binders (LDBs) that bind to bacterial phytochrome DrBphP upon red light (660 nm) exposure.
- Utilized the endogenous mammalian biliverdin chromophore for red light absorption.
- Fused LDBs with single-domain antibodies to target epitope-tagged proteins (e.g., GFP) for light-induced clustering.
Main Results:
- Demonstrated rapid and reversible protein sequestration into light-responsive clusters via R-LARIAT.
- Achieved high light sensitivity, clustering efficiency, and sustained stability.
- Successfully inhibited cell cycle progression in HeLa cells by sequestering tubulin.
Conclusions:
- R-LARIAT provides a novel and effective method for optogenetic control of protein function using red light.
- The system expands the optogenetic toolbox for studying dynamic biological processes with high spatiotemporal resolution.
- Potential applications in living tissues and therapeutic interventions.
