Modular Photoswitchable Molecular Glues for Chemo-Optogenetic Control of Protein Function in Living Cells
Jun Zhang1,2, Laura K Herzog1,2, Dale P Corkery1,2
1SciLifeLab, Department of Chemistry, Umeå University, 90187, Umeå, Sweden.
Angewandte Chemie (International Ed. in English)
|January 8, 2025
Summary
Researchers developed photoswitchable molecular glues (sMGs) for precise, light-controlled manipulation of cellular functions. This versatile chemo-optogenetic system allows reversible switching of protein activity, localization, and levels with high spatiotemporal accuracy.
Area of Science:
- Molecular Biology
- Biochemistry
- Optogenetics
- Chemical Biology
Background:
- Optogenetic systems and chemically induced dimerization/proximity (CID/CIP) are crucial for studying biological dynamics and regulatory networks.
- Existing tools often lack the precise temporal control needed for complex biological investigations.
Purpose of the Study:
- To develop a versatile chemo-optogenetic system using modular, photoswitchable molecular glues (sMGs).
- To enable repeated, light-controlled switching of protein function on and off with high spatiotemporal precision.
Main Methods:
- Rational design of sMGs using molecular dynamics (MD) simulations.
- Incorporation of various photoswitches to customize sMG properties.
- Demonstration of reversible control over protein localization, organelle positioning, protein-fragment complementation, and posttranslational protein levels.
Main Results:
- Successful development of modular, photoswitchable molecular glues (sMGs).
- Demonstrated precise, reversible optical control over diverse cellular processes.
- sMGs exhibit customizable properties based on incorporated photoswitches.
Conclusions:
- The developed chemo-optogenetic system offers sophisticated optical manipulation of cellular processes.
- This versatile platform opens new avenues for research in chemo-optogenetics.
- The system provides high spatiotemporal precision for controlling protein function and cellular events.
