FK506-binding protein 12 (FKBP12) (F36V) domain (FKBP12(F36V))

The FK506-binding protein 12 (FKBP12) (F36V) domain is an engineered variant of the human FKBP12 protein, specifically modified to facilitate chemically induced dimerization (CID) (Di Stasi et al., 2011, NEJM). By replacing the phenylalanine at position 36 with a valine, a "hole" is created in the ligand-binding pocket that accommodates "bumped" synthetic ligands like rimiducid (AP1903) while excluding endogenous FK506 (Clackson et al., 1998, PNAS). This system is widely utilized in synthetic biology and adoptive cell therapies, such as CAR-T cells, to create inducible safety switches or activation mechanisms (Straathof et al., 2005, Blood). For instance, when fused to Caspase-9 (iCasp9), the addition of rimiducid triggers dimerization and subsequent apoptosis of the engineered cells, providing a method to mitigate severe adverse events like graft-versus-host disease or cytokine release syndrome (Di Stasi et al., 2011, NEJM). Beyond safety switches, the domain is also used in "Go-CAR-T" platforms where rimiducid-mediated dimerization of costimulatory domains enhances T-cell activity and persistence (Foster et al., 2017, Molecular Therapy). This engineered domain thus serves as a critical tool for the precise temporal and spatial control of therapeutic cell populations (Spencer et al., 1993, Science).

Other names

FKBP(F36V)FKBP12-F36VDimerization domainiCasp9 domainModified FK506-binding protein 12

Small-molecule induced dimerization of fusion proteins containing the FKBP12(F36V) domain, leading to downstream signaling or enzymatic activation.