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Updated: Aug 6, 2026
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BRET-based G Protein Biosensors for Measuring G Protein-Coupled Receptor Activity in Live Cells
Published on: November 7, 2025
Photoregulation of G protein Ras function using photoresponsive protein
Stanley Tabi Besong1, Ziyun Zhang1, Fofou Yonta Tostani1
1Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-cho, Hachioji, Tokyo, Japan.
Bioscience, Biotechnology, and Biochemistry
|July 22, 2026
Summary
Researchers created a light-controlled Ras protein (PR-Ras) that acts as a molecular switch. Light regulates Ras activity by modulating its interactions with regulatory proteins, not its intrinsic function.
Area of Science:
- Molecular Biology
- Cell Signaling
- Biochemistry
Background:
- The small GTPase Ras is a key regulator of intracellular signaling pathways.
- Ras activity is controlled by its GTP/GDP-bound state, acting as a molecular switch.
- Understanding Ras regulation is crucial for deciphering cellular processes and diseases.
Purpose of the Study:
- To develop a photoregulated Ras (PR-Ras) for precise temporal control of Ras signaling.
- To investigate the mechanism of light-dependent regulation of PR-Ras activity.
- To explore the role of regulatory proteins in PR-Ras photocontrol.
Main Methods:
- Fusion of the photoresponsive LOV2-Jα domain to the N-terminus of Ras.
- Assaying intrinsic GTPase activity and light-dependent regulation in vitro.
- Investigating the influence of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs).
- Utilizing a GEF mutant to disrupt allosteric interactions.
Main Results:
- PR-Ras maintained intrinsic GTPase activity and reversible photoresponsiveness.
- Light-dependent regulation of PR-Ras was observed in the presence of regulatory proteins, particularly GEFs, under specific GAP concentrations.
- Disruption of the Ras-GEF allosteric interaction abolished light-dependent regulation.
- Photocontrol was mediated by modulation of regulatory interactions, not intrinsic catalysis.
Conclusions:
- PR-Ras provides a tool for light-inducible control of Ras signaling.
- The Ras-GEF allosteric interaction is a key mechanism for photocontrol of Ras activity.
- This study offers insights into the allosteric regulation of Ras signaling pathways.
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