Immunophilin

Immunophilins are a highly conserved family of intracellular proteins characterized by their peptidyl-prolyl cis-trans isomerase (PPIase) activity, which facilitates protein folding by catalyzing the interconversion of cis and trans isomers of proline-containing peptide bonds[1][2][3]. The two main immunophilin families are cyclophilins (which bind cyclosporin) and FK506-binding proteins (FKBPs, which bind tacrolimus and sirolimus)[1][4]. These proteins also serve as chaperones, assisting in the folding of other cellular proteins and modulating the function of intracellular calcium channels, such as ryanodine and inositol 1,4,5-trisphosphate (IP3) receptors[2][3]. Immunophilins became therapeutically important targets due to their roles as receptors for key immunosuppressive agents, mediating their effects primarily through inhibition of the phosphatase calcineurin, which blocks T cell activation and cytokine release[1][2]. They have broad biological significance, including roles in immune regulation, intracellular signaling, and potentially in neurological and cardiovascular processes[2][3][4].

Other names

CyclophilinFK506-binding proteinFKBPPeptidyl-prolyl isomeraseCsA-binding proteinCyclosporin-binding protein

Complex formation with immunosuppressive drugs (e.g., CsA, FK506) inhibits the peptidyl-prolyl isomerase activity of immunophilins[1]. Drug-immunophilin complexes bind to and inhibit calcineurin, blocking calcium-dependent T cell activation by preventing interleukin-2 release[1][2]. Modulation of calcium channels through physical association, independent of immunosuppressant binding[3].