Cyclophilins

Cyclophilins are a family of highly conserved proteins that function as peptidyl-prolyl cis-trans isomerases (PPIases). By catalyzing the isomerization of peptide bonds at proline residues, they assist protein folding and conformational maturation. Cyclophilins are also categorized as immunophilins because they bind immunosuppressive drugs such as cyclosporin A, and the drug–protein complex can influence signaling pathways.

Members of the cyclophilin family are widely distributed in eukaryotic cells and show diverse subcellular localization. In humans, examples include PPIA (cyclophilin A) predominantly in the cytosol, PPIB (cyclophilin B) in the endoplasmic reticulum lumen, PPIF (cyclophilin D) in mitochondria, and PPIG (cyclophilin G) in the nucleus. The family also includes PPIL1–PPIL6, as well as PPIH and PPIE, among others. Some cyclophilins associate with chaperone systems such as Hsp90 and participate in broader regulatory networks beyond simple isomerization.

Biologically, cyclophilins contribute to protein folding, folding quality control, and the regulation of signaling pathways. They can influence immune responses, RNA processing, and stress reactions. Certain members have been implicated in the life cycles of various viruses, where they may affect viral replication or entry. A well-known mechanism involving a cyclophilin is its interaction with cyclosporin A; the resulting complex inhibits calcineurin, suppressing T-cell activation and providing a basis for some immunosuppressive therapies. Tacrolimus, by contrast, binds FKBP proteins rather than cyclophilins.

Overall, cyclophilins constitute a versatile protein family with essential roles in proteostasis and cellular signaling, as well as significant relevance to medicine and virology.