Design and Application of Novel Ligand-Induced Split-Protein Systems

This invention is a split protein system that functions as a biotechnological chemically-induced dimerization (CID) tool. These CID systems are useful for biological research to control numerous outputs in living organisms such as inducing the activation of a specific protein, protein localization, and inducing transcription. This novel CID system can be used to stabilize a newly designed ternary complex.

Background:
CID is a biotechnological method where two or more proteins can bind with one another and form a ternary or higher complex only in the presence of a specific small molecule or other dimerizing ligand. These different ligands in CID systems can be engineered to induce activation of protein outcomes that can be used to control a variety of signaling pathways and their related physiological outputs and thus be used to study biology and treat diseases. The present invention features a novel approach for the engineering of new CID systems based on the recognition that ligand binding may stabilize a newly designed ternary complex.  

Applications:

• Study activation of proteins for controlling signaling pathways and outcomes
• Develop novel therapeutics based on protein activation and control of signaling pathways

Advantages:

• New tool for designing and building ternary complexes for targeted protein activation
• New tool for designing and building protein-ligand complexes for protein engineering technology
• Builds on split luciferase assay technology