Cyclophilin
Encyclopedia
Cyclophilins are a family of protein
s from vertebrates and other organism
s that bind to cyclosporine, an immunosuppressant
which is usually used to suppress rejection
after internal organ transplant
s . 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 throughout the cell, including the ER, and some are even secreted.
also known as peptidylprolyl isomerase A, 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 ciclosporin
-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 is also known to be recruited by the Gag polyprotein during HIV-1 virus infection, and its incorporation into new virus particles is essential for HIV-1 infectivity.
, which is located in the matrix
of mitochondria, is a component of the mitochondrial permeability transition pore
. The pore opening raises the permeability of the mitochondrial inner membrane, allows influx of cytosol
ic 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 (CsA), which binds to CyP-D, inhibits the pore opening.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s from vertebrates and other organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
s that bind to cyclosporine, an immunosuppressant
Immunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
which is usually used to suppress rejection
Transplant rejection
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after...
after internal organ transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
s . These proteins have peptidyl prolyl isomerase
Prolyl isomerase
Prolyl isomerase is an enzyme found in both prokaryotes and eukaryotes that interconverts the cis and trans isomers of peptide bonds with the amino acid proline. Proline has an unusually conformationally restrained peptide bond due to its cyclic structure with its side chain bonded to its...
activity, which catalyzes
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the isomerization of peptide bonds from trans form to cis form at proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
residues and facilitates protein folding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
.
Cyclophilin A is a cytosolic
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
and highly abundant protein. The protein belongs to a family of isozymes, including cyclophilins B and C, and natural killer cell
Cell
-Science and technology:*Cell , the functional basic unit of life*Cell , a term used in an electronic circuit design schematics*Cell , a three-dimensional element, part of a higher-dimensional object*Cell , a scientific journal...
cyclophilin-related protein. Major isoforms have been found throughout the cell, including the ER, and some are even secreted.
Cyclophilin A (CycA)
Cyclophilin APeptidylprolyl isomerase A
Peptidylprolyl isomerase A also known as cyclophilin A or rotamase A is an enzyme that in humans is encoded by the PPIA gene.- Function :...
also known as peptidylprolyl isomerase A, which is found in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
, has a beta barrel
Beta barrel
A beta barrel is a large beta-sheet that twists and coils to form a closed structure in which the first strand is hydrogen bonded to the last.Beta-strands in beta-barrels are typically arranged in an antiparallel fashion...
structure with two alpha helices
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
and a beta-sheet. Other cyclophilins have similar structures to cyclophilin A. The ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
-cyclophilin A complex inhibits a calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
/calmodulin
Calmodulin
Calmodulin is a calcium-binding protein expressed in all eukaryotic cells...
-dependent phosphatase
Phosphatase
A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...
, calcineurin
Calcineurin
Calcineurin is a protein phosphatase also known as protein phosphatase 3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B . It activates the T cells of the immune system and can be blocked by drugs...
, the inhibition of which is thought to suppress organ rejection by halting the production of the pro-inflammatory molecules TNF alpha and interleukin 2
Interleukin 2
Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
.
Cyclophilin A is also known to be recruited by the Gag polyprotein during HIV-1 virus infection, and its incorporation into new virus particles is essential for HIV-1 infectivity.
Cyclophilin D
Cyclophilin DPPID
Peptidylprolyl isomerase D , also known as PPID, is an enzyme which in humans is encoded by the PPID gene.- Function :...
, which is located in the matrix
Mitochondrial matrix
In the mitochondrion, the matrix contains soluble enzymes that catalyze the oxidation of pyruvate and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes. The word "matrix" stems from the fact that this space is viscous, compared to the...
of mitochondria, is a component of the mitochondrial permeability transition pore
Mitochondrial permeability transition pore
The Mitochondrial Permeability Transition, or MPT, is defined as an increase in the permeability of the mitochondrial membranes to molecules of less than 1500 Daltons in molecular weight. MPT results from the opening of a mitochondrial permeability transition pore, also known as the MPT pore or MPTP...
. The pore opening raises the permeability of the mitochondrial inner membrane, allows influx of cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
ic molecules into the mitochondrial matrix
Mitochondrial matrix
In the mitochondrion, the matrix contains soluble enzymes that catalyze the oxidation of pyruvate and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes. The word "matrix" stems from the fact that this space is viscous, compared to the...
, 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 (CsA), which binds to CyP-D, inhibits the pore opening.
Examples
Human genes encoding proteins containing the cyclophilin type peptidyl-prolyl cis-trans isomerase domain include:- PPIA, PPIBPPIBPeptidyl-prolyl cis-trans isomerase B is an enzyme that in humans is encoded by the PPIB gene.-Interactions:PPIB has been shown to interact with Apolipoprotein B.-Further reading:...
, PPICPPICPeptidyl-prolyl cis-trans isomerase C is an enzyme that in humans is encoded by the PPIC gene.-Further reading:...
, PPIDPPIDPeptidylprolyl isomerase D , also known as PPID, is an enzyme which in humans is encoded by the PPID gene.- Function :...
, PPIEPPIE (gene)Peptidyl-prolyl cis-trans isomerase E is an enzyme that in humans is encoded by the PPIE gene.-Interactions:PPIE has been shown to interact with MLL.-Further reading:...
, PPIFPPIFPeptidyl-prolyl cis-trans isomerase, mitochondrial is an enzyme that in humans is encoded by the PPIF gene.-Further reading:...
, PPIGPPIG (gene)Peptidyl-prolyl cis-trans isomerase G is an enzyme that in humans is encoded by the PPIG gene.-Interactions:PPIG has been shown to interact with Pinin.-Further reading:...
, PPIHPPIHPeptidyl-prolyl cis-trans isomerase H is an enzyme that in humans is encoded by the PPIH gene.-Further reading:... - PPIL1PPIL1Peptidyl-prolyl cis-trans isomerase-like 1 is an enzyme that in humans is encoded by the PPIL1 gene.-Further reading:...
, PPIL2PPIL2Peptidyl-prolyl cis-trans isomerase-like 2 is an enzyme that in humans is encoded by the PPIL2 gene.-Further reading:...
, PPIL3PPIL3Peptidyl-prolyl cis-trans isomerase-like 3 is an enzyme that in humans is encoded by the PPIL3 gene.-Further reading:...
, PPIL4PPIL4Peptidyl-prolyl cis-trans isomerase-like 4 is an enzyme that in humans is encoded by the PPIL4 gene.-Further reading:...
, PPIAL4, PPIL6 - PPWD1