Cyclophilin


Cyclophilin
peptidylprolyl isomerase A (cyclophilin A)
Cyclophilin A-cyclosporin complex 1CWA.png
Ribbon diagram of cyclophilin A in complex with ciclosporin (yellow). From PDB 1CWA.
Identifiers
Symbol PPIA
Entrez 5478
HUGO 9253
OMIM 123840
RefSeq NM_203430
UniProt Q3KQW3
Other data
EC number 5.2.1.8
Locus Chr. 7 p13
Pro_isomerase
PDB 1w74 EBI.jpg
x-ray structure of peptidyl-prolyl cis-trans isomerase a, ppia, rv0009, from mycobacterium tuberculosis.
Identifiers
Symbol Pro_isomerase
Pfam PF00160
Pfam clan CL0475
InterPro IPR002130
PROSITE PDOC00154
SCOP 1cyh

Cyclophilins are a family of proteins from vertebrates and other organisms that bind to cyclosporine, an immunosuppressant which is usually used to suppress rejection after internal organ transplants [1]. 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.[2][3][4] Major isoforms have been found throughout the cell, including the ER, and some are even secreted.

Contents

Cyclophilin A (CycA)

Cyclophilin A 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.

Cyclophilin D

Cyclophilin D, 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 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 (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:

References

  1. ^ Stamnes MA, Rutherford SL, Zuker CS (September 1992). "Cyclophilins: a new family of proteins involved in intracellular folding". Trends Cell Biol. 2 (9): 272–6. doi:10.1016/0962-8924(92)90200-7. PMID 14731520. 
  2. ^ Trandinh CC, Pao GM, Saier MH (December 1992). "Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl-prolyl cis-trans isomerases". FASEB J. 6 (15): 3410–20. PMID 1464374. 
  3. ^ Galat A (September 1993). "Peptidylproline cis-trans-isomerases: immunophilins". Eur. J. Biochem. 216 (3): 689–707. doi:10.1111/j.1432-1033.1993.tb18189.x. PMID 8404888. 
  4. ^ Hacker J, Fischer G (November 1993). "Immunophilins: structure-function relationship and possible role in microbial pathogenicity". Mol. Microbiol. 10 (3): 445–56. doi:10.1111/j.1365-2958.1993.tb00917.x. PMID 7526121. 

External links


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Look at other dictionaries:

  • cyclophilin — Enzyme with PPIase activity; binds the immunosuppressive drug cyclosporin A. See immunophilin …   Dictionary of molecular biology

  • cyclophilin — noun Any of a class of proteins that bind to ciclosporin …   Wiktionary

  • CYPA — cyclophilin A …   Medical dictionary

  • CYPC — cyclophilin C …   Medical dictionary

  • CYPH — cyclophilin …   Medical dictionary

  • CYPA — • cyclophilin A …   Dictionary of medical acronyms & abbreviations

  • CYPC — • cyclophilin C …   Dictionary of medical acronyms & abbreviations

  • CYPH — • cyclophilin …   Dictionary of medical acronyms & abbreviations

  • CYP — • cyclophilin; • cyproheptadine; • cytochrome P …   Dictionary of medical acronyms & abbreviations

  • Peptidylprolyl isomerase A — (cyclophilin A) PDB rendering based on 1ak4 …   Wikipedia


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