Function
Cyclophilin (Cyp) binds cyclosporin. They are peptidylprolyl isomerases which catalyze the isomerisation of proline. The Cyp-A/cyclosporin A complex inhibits organ rejection. Cyp-D is a component of the mitochondria permeability pore. Rotamase such as FKBP is a prokaryotic Cyp which is not inhibited by cyclosporin but by FK-506 – an immunosuppressive drug. [1] See also Isomerases.
- Cyclophilin-A has peptide cis-trans isomerase activity which regulates protein folding and trafficking[2] .
- Cyclophilin-B interacts with HCV RNA polymerase and stimulates its RNA binding activity[3] .
- Cyclophilin-C is a component of US2-mediated immune invasion[4] .
- Cyclophilin-D is a regulator of the mitochondrial permeability transition pore[5] .
- Cyclophilin-E has a role in osteoblast differentiation by increasing the transcriptional activity of Runx2[6] .
- Cyclophilin-H mediates interactions between different proteins inside the spliceosome[7] .
- Cyclophilin-J has upregulated expression in human glioma[8] .
- Cyclophilin-38 stabilises photosystem II in chloroplasts and supports root growth[9] .
- Cyclophilin-40 modulates steroid receptor function through its association with Hsp90[10] .
Relevance
Cyp-A has a key role in immunosuppression and viral infection[11]. Cyp-A is the target of the immunosuppressant cyclosporin A whose binding leads to the suppression of the T-cell mediated immune response. Cyp-A is required for effective HIV-1 replication in host cells[12].
Structural highlights
. The acetylation modulates key functions of Cyp-A activity.[13]
3D Structures of Cyclophilin
Cyclophilin 3D structures
