Cyclophilins: The Structure and Functions of an Important Peptidyl-prolyl Isomerase
International Journal of Biochemistry, Biophysics & Molecular Biology
Volume 4, Issue 1, June 2019, Pages: 1-6
Received: May 2, 2019;
Accepted: Jun. 5, 2019;
Published: Jun. 28, 2019
Views 122 Downloads 23
Mukhtar Idris, Laboratory of Computational Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China
Mujeebat Idris, Department of Chemical Sciences, Olabisi Onabanjo University, Ago-iwoye, Nigeria
Fadahunsi Adeola, Department of Biomedical Engineering, School of Life Sciences, University of Science and Technology of China, Hefei, China
Divine Mensah Sedzro, Laboratory of Cellular Dynamics, School of Life Sciences, University of Science and Technology of China, Hefei, China
Cyclophilins are a subgroup of highly conserved protein family immunophilins which are peptidyl-prolyl isomerases that interconvert between the cis and trans positions. They can act as chaperones in maintaining conformational quality control of proteomes. They are structurally conserved throughout evolution and have been found in mammals, plants, insects, fungi, and bacteria. They share a common fold architecture consisting of 8 antiparallel beta sheets and two alpha helices that pack against the sheets. They exist in the cellular compartment of most tissues and encode special functions. Intracellular Cyclophilins are secreted from cells in response to inflammatory stimuli and can mediate intercellular communication. Pro-inflammatory signals may be stimulated by extracellular Cyclophilin. Overexpression of Cyclophilins can contribute to pathological conditions. Cyclophilins are involved in the pathogenesis of viral infection, neurodegenerative diseases, ageing and cancer. Exhibiting several molecular functions, Cyclophilins can bind to cyclosporine and calcium-dependent ser/thr Calcineurin and has been used to describe the immunosuppressive action of cyclosporine. Cyclophilin can stabilize the cis-trans conformation transition state and speed up isomerization steps in protein folding. This process is important in the assembly of multiple domain proteins. Their existence as foldases and molecular chaperones enable them to be able to assist in the covalent folding or unfolding and the assembly or disassembly of other macromolecular structures.
Divine Mensah Sedzro,
Cyclophilins: The Structure and Functions of an Important Peptidyl-prolyl Isomerase, International Journal of Biochemistry, Biophysics & Molecular Biology.
Vol. 4, No. 1,
2019, pp. 1-6.
Schmid, F. X., Prolyl isomerase: enzymatic catalysis of slow protein-folding reactions. Annual review of biophysics and biomolecular structure, 1993. 22 (1): p. 123-143.
Bell, A., P. Monaghan, and A. P. Page, Peptidyl-prolyl cis–trans isomerases (immunophilins) and their roles in parasite biochemistry, host–parasite interaction and antiparasitic drug action. International journal for parasitology, 2006. 36 (3): p. 261-276.
Sokolskaja, E. and J. Luban, Cyclophilin, TRIM5, and innate immunity to HIV-1. Current opinion in microbiology, 2006. 9 (4): p. 404-408.
Rahfeld, J.-U., et al., A novel peptidyl‐prolyl cisltrans isomerase from Escherichia coli. FEBS letters, 1994. 343 (1): p. 65-69.
Missiakas, D., J. M. Betton, and S. Raina, New components of protein folding in extracytoplasmic compartments of Escherichia coli SurA, FkpA and Skp/OmpH. Molecular microbiology, 1996. 21 (4): p. 871-884.
Galat, A., Peptidylprolyl cis/trans isomerases (immunophilins): biological diversity-targets-functions. Current topics in medicinal chemistry, 2003. 3 (12): p. 1315-1347.
Göthel, S. F. and M. Marahiel, Peptidyl-prolyl cis-trans isomerases, a superfamily of ubiquitous folding catalysts. Cellular and Molecular Life Sciences CMLS, 1999. 55 (3): p. 423-436.
Arevalo-Rodriguez, M., et al., Prolyl isomerases in yeast. Front. Biosci, 2004. 9 (1-3): p. 2420-2446.
Pemberton, T. J., Identification and comparative analysis of sixteen fungal peptidyl-prolyl cis/trans isomerase repertoires. BMC genomics, 2006. 7 (1): p. 244.
Wang, P. and J. Heitman, The cyclophilins. Genome biology, 2005. 6 (7): p. 226.
Mainali, H. R., P. Chapman, and S. Dhaubhadel, Genome-wide analysis of Cyclophilin gene family in soybean (Glycine max). BMC plant biology, 2014. 14 (1): p. 282.
Kumari, S., et al., Expression of a cyclophilin OsCyp2-P isolated from a salt-tolerant landrace of rice in tobacco alleviates stress via ion homeostasis and limiting ROS accumulation. Functional & integrative genomics, 2015. 15 (4): p. 395-412.
Trivedi, D. K., et al., Genome wide analysis of Cyclophilin gene family from rice and Arabidopsis and its comparison with yeast. Plant signaling & behavior, 2012. 7 (12): p. 1653-1666.
Andreeva, L., R. Heads, and C. J. Green, Cyclophilins and their possible role in the stress response. International journal of experimental pathology, 1999. 80 (6): p. 305-315.
Haendler, B., et al., Yeast cyclophilin: isolation and characterization of the protein, cDNA and gene. Gene, 1989. 83 (1): p. 39-46.
Kang, C. B., et al., FKBP family proteins: immunophilins with versatile biological functions. Neurosignals, 2008. 16 (4): p. 318-325.
Howard, B. R., et al., Structural insights into the catalytic mechanism of cyclophilin A. Nature Structural & Molecular Biology, 2003. 10 (6): p. 475.
Davis, T. L., et al., Structural and biochemical characterization of the human cyclophilin family of peptidyl-prolyl isomerases. PLoS biology, 2010. 8 (7): p. e1000439.
Hoffmann, K. and R. E. Handschumacher, Cyclophilin-40: evidence for a dimeric complex with hsp90. Biochemical Journal, 1995. 307 (1): p. 5-8.
Reidt, U., et al., Crystal structure of a complex between human spliceosomal cyclophilin H and a U4/U6 snRNP-60K peptide. Journal of molecular biology, 2003. 331 (1): p. 45-56.
Jin, L. and S. C. Harrison, Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin. Proceedings of the National Academy of Sciences, 2002. 99 (21): p. 13522-13526.
Mikol, V., et al., X-ray structure of a monomeric cyclophilin A-cyclosporin A crystal complex at 2· 1 Å resolution. Journal of molecular biology, 1993. 234 (4): p. 1119-1130.
Rao, A., C. Luo, and P. G. Hogan, Transcription factors of the NFAT family: regulation and function. Annual review of immunology, 1997. 15 (1): p. 707-747.
Lei, B., et al., Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis. Nature medicine, 2001. 7 (12): p. 1298.
Walker, K. W. and H. F. Gilbert, Scanning and escape during protein-disulfide isomerase-assisted protein folding. Journal of Biological Chemistry, 1997. 272 (14): p. 8845-8848.
Göthel, S. F., M. Herrler, and M. A. Marahiel, Peptidyl− Prolyl Cis− Trans Isomerase of Bacillus subtilis: Identification of Residues Involved in Cyclosporin A Affinity and Catalytic Efficiency. Biochemistry, 1996. 35 (11): p. 3636-3640.
Freeman, B. C., D. O. Toft, and R. I. Morimoto, Molecular chaperone machines: chaperone activities of the cyclophilin Cyp-40 and the steroid aporeceptor-associated protein p23. Science, 1996. 274 (5293): p. 1718-1720.
Towers, G., et al., A conserved mechanism of retrovirus restriction in mammals. Proceedings of the National Academy of Sciences, 2000. 97 (22): p. 12295-12299.
Gamble, T. R., et al., Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid. Cell, 1996. 87 (7): p. 1285-1294.
Gitti, R. K., et al., Structure of the amino-terminal core domain of the HIV-1 capsid protein. Science, 1996. 273 (5272): p. 231-235.
Bosco, D. A., et al., Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A. Proceedings of the National Academy of Sciences, 2002. 99 (8): p. 5247-5252.
Braaten, D., H. Ansari, and J. Luban, The hydrophobic pocket of cyclophilin is the binding site for the human immunodeficiency virus type 1 Gag polyprotein. Journal of virology, 1997. 71 (3): p. 2107-2113.
Stoller, G., et al., A ribosome‐associated peptidyl‐prolyl cis/trans isomerase identified as the trigger factor. The EMBO journal, 1995. 14 (20): p. 4939-4948.
Mi, H., et al., A nuclear RNA-binding cyclophilin in human T cells. FEBS letters, 1996. 398 (2-3): p. 201-205.
Wang, T., et al., 1. 88 Å crystal structure of the C domain of hCyP33: A novel domain of peptidyl-prolyl cis–trans isomerase. Biochemical and biophysical research communications, 2005. 333 (3): p. 845-849.
Zorio, D. A. and T. Blumenthal, Both subunits of U2AF recognize the 3′ splice site in Caenorhabditis elegans. Nature, 1999. 402 (6763): p. 835.
Adams, B., et al., A novel class of dual-family immunophilins. Journal of Biological Chemistry, 2005. 280 (26): p. 24308-24314.
Yurchenko, V., et al., Active site residues of cyclophilin A are crucial for its signaling activity via CD147. Journal of Biological Chemistry, 2002. 277 (25): p. 22959-22965.
Biswas, C., et al., The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer research, 1995. 55 (2): p. 434-439.
Kasinrerk, W., N. Tokrasinwit, and P. Phunpae, CD147 monoclonal antibodies induce homotypic cell aggregation of monocytic cell line U937 via LFA-1/ICAM-1 pathway. Immunology, 1999. 96 (2): p. 184.
Saleh, T., et al., Cyclophilin A promotes cell migration via the Abl-Crk signaling pathway. Nature chemical biology, 2016. 12 (2): p. 117.