Diversified targets of FKBP25 and its complex with rapamycin

• We have solved the structure of the C-terminal FKBD of mFKBP25 bound to the immunosuppressive drug rapamycin.
• We show that mFKBP25 and its complex with rapamycin binds to different DNAs and. RNAs.
• We have shown that the mFKBP25/rapamycin complex binds to calcineurin phosphatase.
• We have shown that mFKBP25/rapamycin binds to elongation factor 1β, a crucial factor in protein synthesis and to several other nuclear proteins.

FKBP25 is a member of the super-family of peptidylprolyl cis/trans isomerases, which is a high affinity binder for the immunosuppressive antibiotic rapamycin (Rpm). FKBP25 isolated from natural sources, its recombinant murine homologue (mFKBP25) and their complexes with rapamycin bind to diverse DNAs, RNAs and heparin affinity beads. The recombinant mFKBP25/rapamycin complex binds to several proteins including the calcineurin–A/calcineurin–B/calmodulin complex and to elongation factor 1β. We solved the X-ray structure of the C-terminal domain of mFKBP25 bound to rapamycin that has a higher resolution than of its human counterpart, and which clearly illustrates that the positively charged 40s loop is an epitope of the FK506-like binding domain (FKBD) for interactions with various biopolymers.