immunophilin

Immunophilins are a family of intracellular proteins that bind to immunosuppressive drugs. They are characterized by their ability to interact with specific drugs, such as cyclosporine, FK506 (tacrolimus), and rapamycin. These drugs, when bound to their respective immunophilins, form complexes that inhibit crucial cellular processes, particularly in immune cells.

The primary function of immunophilins is thought to be related to protein folding and trafficking. They possess peptidyl-prolyl cis-trans isomerase activity, meaning they can catalyze the isomerization of proline residues in proteins. This catalytic activity is important for proper protein folding and the maturation of various cellular proteins. Some immunophilins also function as molecular chaperones, assisting in the folding and assembly of other proteins.

There are three main families of immunophilins: cyclophilins, FK506-binding proteins (FKBP), and parvulins. Cyclophilins bind to cyclosporine, while FKBPs bind to FK506 and rapamycin. Parvulines are a smaller family that also exhibits peptidyl-prolyl cis-trans isomerase activity.

The immunosuppressive action of drugs like cyclosporine and FK506 arises from the immunophilin-drug complexes. For instance, the cyclosporine-cyclophilin complex inhibits calcineurin, a key enzyme in T-cell activation. Similarly, the FK506-FKBP complex inhibits calcineurin. Rapamycin, when bound to FKBP, forms a complex that inhibits the mammalian target of rapamycin (mTOR) signaling pathway, which is involved in cell growth and proliferation.

Beyond their role in immunosuppression, immunophilins are implicated in a variety of other cellular functions, including gene transcription, cell signaling, and protein transport. Their diverse roles highlight their importance in maintaining cellular homeostasis and responding to various stimuli.