FK506 Binding Protein 4 (FKBP4), also known as FKBP52, is a member of the immunophilin protein family. This family of proteins is involved in immunoregulation and essential cellular processes such as protein folding and trafficking . FKBP4 is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 (tacrolimus) and rapamycin .
FKBP4 is characterized by its ability to catalyze the cis-trans isomerization of proline residues in proteins, which is crucial for proper protein folding. This protein contains multiple domains, including the FK506-binding domain and the tetratricopeptide repeat (TPR) domain. The TPR domain is involved in protein-protein interactions and is essential for the protein’s role as a co-chaperone in the heat shock protein 90 (Hsp90) complex .
FKBP4, along with other FKBPs, plays a significant role in immunoregulation by binding to immunosuppressive drugs. The FKBP-FK506 complex inhibits the phosphatase activity of calcineurin, thereby blocking the activation of T-cells and preventing immune responses . This mechanism is particularly important in preventing organ rejection in transplant patients and treating autoimmune diseases .
Beyond its role in immunoregulation, FKBP4 is involved in various cellular processes. It acts as a co-chaperone with Hsp90, assisting in the proper folding and stabilization of steroid hormone receptors and other client proteins . FKBP4 also plays a role in the trafficking of proteins within the cell, ensuring that they reach their correct destinations .
The recombinant form of FKBP4, expressed in Escherichia coli, is widely used in research to study its structure and function. This recombinant protein is valuable for investigating the molecular mechanisms underlying its interactions with immunosuppressive drugs and its role in cellular processes . Additionally, FKBP4 is a potential target for therapeutic interventions in diseases related to protein misfolding and trafficking .