|Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD|
Ribbon diagram of cyclophilin A in complex with ciclosporin (yellow). From .
|SCOPe||1cyh / SUPFAM|
Cyclophilins (CYPs) are a family of proteins named after their ability to bind to ciclosporin (cyclosporin A), an immunosuppressant which is usually used to suppress rejection after internal organ transplants. They are found in all domains of life. These proteins have peptidyl prolyl isomerase activity, which catalyzes the isomerization of peptide bonds from trans form to cis form at proline residues and facilitates protein folding.
Cyclophilin A is a cytosolic and highly abundant protein. The protein belongs to a family of isozymes, including cyclophilins B and C, and natural killer cell cyclophilin-related protein. Major isoforms have been found within single cells, including inside the Endoplasmic reticulum, and some are even secreted.
Human genes encoding proteins containing the cyclophilin domain include:
Cyclophilin A (CYPA) also known as peptidylprolyl isomerase A (PPIA), which is found in the cytosol, has a beta barrel structure with two alpha helices and a beta-sheet. Other cyclophilins have similar structures to cyclophilin A. The cyclosporin-cyclophilin A complex inhibits a calcium/calmodulin-dependent phosphatase, calcineurin, the inhibition of which is thought to suppress organ rejection by halting the production of the pro-inflammatory molecules TNF alpha and interleukin 2.
Cyclophilin D (PPIF, note that literature is confusing, the mitochondrial cyclophilin is encoded by the PPIF gene), which is located in the matrix of mitochondria, is only a modulatory, but may or may not be a structural component of the mitochondrial permeability transition pore. The pore opening raises the permeability of the mitochondrial inner membrane, allows influx of cytosolic molecules into the mitochondrial matrix, increases the matrix volume, and disrupts the mitochondrial outer membrane. As a result, the mitochondria fall into a functional disorder, so the opening of the pore plays an important role in cell death. Cyclophilin D is thought to regulate the opening of the pore because cyclosporin A, which binds to CyP-D, inhibits the pore opening.
Cyclophilins as drug targets
This section needs expansion. You can help by adding to it. (December 2015)
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