1. Structural insights into rapamycin-induced oligomerization of a FRB-FKBP fusion protein.
- Author
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Inobe T, Sakaguchi R, Obita T, Mukaiyama A, Koike S, Yokoyama T, Mizuguchi M, and Akiyama S
- Subjects
- Humans, Crystallography, X-Ray, Models, Molecular, Protein Domains, Protein Binding, Sirolimus chemistry, Sirolimus pharmacology, Sirolimus metabolism, Tacrolimus Binding Proteins chemistry, Tacrolimus Binding Proteins metabolism, Tacrolimus Binding Proteins genetics, Protein Multimerization drug effects, Recombinant Fusion Proteins metabolism, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins genetics
- Abstract
Inducible dimerization systems, such as rapamycin-induced dimerization of FK506 binding protein (FKBP) and FKBP-rapamycin binding (FRB) domain, are widely employed chemical biology tools to manipulate cellular functions. We previously advanced an inducible dimerization system into an inducible oligomerization system by developing a bivalent fusion protein, FRB-FKBP, which forms large oligomers upon rapamycin addition and can be used to manipulate cells. However, the oligomeric structure of FRB-FKBP remains unclear. Here, we report that FRB-FKBP forms a rotationally symmetric trimer in crystals, but a larger oligomer in solution, primarily tetramers and pentamers, which maintain similar inter-subunit contacts as in the crystal trimer. These findings expand the applications of the FRB-FKBP oligomerization system in diverse biological events., (© 2024 Federation of European Biochemical Societies.)
- Published
- 2024
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