Cyclophilins are known for their ability to bind ciclosporin, which is used to suppress rejection after a human has an internal organ transplant. They are found in all kinds of life from animals, to humans, to plants. The fact that they are found in all domains of life highlights just how vital they are to some natural processes such as the cell cycle. Cyclophilins have peptidyl-prolyl cis-trans isomerase activity, and these proteins are collectively known as immunophilins. Humans are thought to have around 16 of these cyclophilins.
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 A has also been linked to a number of diseases in humans when overexpression takes place. Some of these are poor responses to inflammatory diseases, aging, and the progression of certain types of cancer.
Cyclophilin D, is found in the matrix of the mitochondria. This is thought to be a structural component of the mitochondrial permeability transition pore which forms under certain traumatic conditions in the human body such as a heart attack or a stroke. A whole process takes place from the formation of this protein, which is vital when it comes to cell death as it allows an influx of cytosolic molecules which disrupts the mitochondrial outer membrane.
Cyclophilin A is recruited by the Gag polyprotein during HIV-1 virus infection, and its incorporation into new virus particles is essential for it to start infecting the body. However, inhibitors of cyclophilin are now being developed to treat certain neuro diseases, and could even be an effective treatment for liver diseases. The formation of CypA–CsA, a byproduct of cyclophilin and cyclosporine, inhibits the transcription of immune response-related genes and prevents the proliferation of T cells. It is a catalytic protein and it can bind with certain other proteins.
Cyclophilins 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 highly abundant, cytosolic protein that belongs to a family of isozymes. There are some major isoforms that have been found within single cells, and some of these are even secreted.
Cyclophilin A has a beta barrel structure (two alpha helices and a beta sheet). There is usually a crystal-like structure to this protein which is shared by all the variants of cyclophilin. The structure provides an interesting insight into the family tree of this protein and allows researchers to look for diversity among them rather than just similarities.