Protein dimerization plays an important role in a range of cellular processes. Some protein dimerization processes are mediated through the presence of small molecule ligands. A prominent protein-protein interaction induced by a small molecule is the formation of a ternary complex between FKBP12, FRB, and rapamycin. In nature, FK506-binding protein (FKBP12) and FKBP12-rapamycin-associated protein (FRAP), dimerize in the presence of rapamycin and inhibit FRAP kinase activity. Because this interaction is well characterized, it has been extensively used in small molecule-control of protein function. Here, we apply this system to photochemically control DNA recombination and protease activity using split enzymes. The inactive halves of these enzymes were fused to FKBP12 and the FRAP rapamycin-binding domain (FRB) in conjunction with a photocaged rapamycin. Upon UV irradiation, rapamycin is activated and induces an FKBP12 and FRB interaction, bringing the DNA recombinase or protease fragments together, thereby activating their function in live mammalian cells.

Photocaged rapamycin: A new tool for the light-regulation of biological processes

243rd National Meeting (2012)

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