FK506-binding protein family (FKBP)

The FK506-binding protein (FKBP) family comprises a group of proteins characterized by their peptidyl-prolyl cis-trans isomerase (PPIase) activity, which is essential for proper protein folding and trafficking (UniProt, 2023). While FKBP12 is the most prominent member due to its role in mediating the effects of immunosuppressants, other family members like FKBP51 and FKBP52 are vital regulators of steroid hormone receptor sensitivity and cellular stress responses (PubMed, 2021). These proteins act as molecular chaperones and are involved in diverse signaling pathways, including those governing calcium release through ryanodine receptors and the inhibition of the mechanistic target of rapamycin (mTOR) (NIH, 2022). Dysregulation of various FKBP isoforms is linked to a wide range of pathologies, including chronic inflammation, various cancers, and neurodegenerative conditions such as Alzheimer's disease (Nature Reviews Drug Discovery, 2020). Pharmacologically, FKBPs are targeted by macrolide antibiotics like tacrolimus and rapamycin, which utilize the proteins as adapters to inhibit specific signaling enzymes like calcineurin. Recent drug discovery efforts have also focused on selective inhibitors of "other" FKBPs, such as FKBP51, to treat depression and post-traumatic stress disorder (Journal of Biological Chemistry, 2019).

Other names

FK506-binding proteinsImmunophilinsPeptidyl-prolyl cis-trans isomerasesPPIases

Drugs bind to the FKBP domain, often forming a ternary complex that inhibits downstream effectors such as calcineurin or mTOR, or modulating the activity of associated proteins like steroid receptors.