Rapamycin-induced oligomer formation system of FRB–FKBP fusion proteins

• Fusion proteins containing FRB and FKBP formed oligomers on adding rapamycin.
• Various oligomers were generated by adjusting the configuration of fusion proteins.
• FRB–FKBP fusion protein without a linker (FR–FK) specifically formed a tetramer.
• Proteins fused to FR–FK also formed a tetramer.

Most proteins form larger protein complexes and perform multiple functions in the cell. Thus, artificial regulation of protein complex formation controls the cellular functions that involve protein complexes. Although several artificial dimerization systems have already been used for numerous applications in biomedical research, cellular protein complexes form not only simple dimers but also larger oligomers. In this study, we showed that fusion proteins comprising the induced heterodimer formation proteins FRB and FKBP formed various oligomers upon addition of rapamycin. By adjusting the configuration of fusion proteins, we succeeded in generating an inducible tetramer formation system. Proteins of interest also formed tetramers by fusing to the inducible tetramer formation system, which exhibits its utility in a broad range of biological applications.