Skip to main content

Advertisement

Log in

Molecular and biochemical characterization of a protein cyclophilin from the nematode Haemonchus contortusP

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

We have cloned, sequenced and expressed a gene of Haemonchus contortus that encodes a protein (termed HcCYP) consisting of a cyclophilin domain and an RNA recognition motif (RRM). An antiserum raised against the recombinant protein showed that HcCYP was present in the insoluble fraction (mostly nuclear) of the parasite homogenate. The recombinant protein possessed the typical cis-trans peptidyl-prolyl isomerase activity of cyclophilins and this activity was inhibited by the immunosuppressant cyclosporin A. The N-terminal portion of the molecule, carrying the RRM, was able to bind to nucleic acids, whereas the C-terminal portion did not have any binding activity. The possible function of HcCYP in the parasite is discussed on the basis of information available on similar proteins in other organisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Galat A (2003) Peptidylprolyl cis/trans isomerases (immunophilins): Biological diversity – targets – functions. Curr Top Med Chem 3:1315–1347

    CAS  PubMed  Google Scholar 

  2. Handschumacher RE, Harding MW, Rice J, Drugge RJ (1984) Cyclophilin: a specific cytosolic binding protein for Cyclosporin A. Science 226:544–547

    CAS  PubMed  Google Scholar 

  3. Takahashi N, Hayano T, Suzuki M (1989) Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature 337:473–475

    CAS  PubMed  Google Scholar 

  4. Freskgard PO, Bergenhem N, Jonsson BH, Svensson M, Carlsson U (1992) Isomerase and chaperone activity of prolyl isomerase in the folding of carbonic anhydrase. Science 258(5081):466–468

    CAS  PubMed  Google Scholar 

  5. Baker EK, Colley NJ, Zuker CS (1994) The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin. EMBO J 13:4886–4895

    CAS  PubMed  Google Scholar 

  6. Harding MW, Galat A, Uehling DE, Schreiber SL (1989) A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase. Nature 341:758–760

    CAS  PubMed  Google Scholar 

  7. Klinkert MQ, Bugli F, Engels B, Carrasquillo E, Valle C, Cioli D (1995) Characterization of a Schistosoma mansoni cDNA encoding a B-like cyclophilin and its expression in Escherichia coli. Mol Biochem Parasitol 75:99–111

    CAS  PubMed  Google Scholar 

  8. Vaitukaitis J, Robbins JB, Nieschlag E, Ross GT (1971) A method for producing specific antisera with small doses of immunogen. J Clin Endocr 33:983–991

    PubMed  Google Scholar 

  9. Sugita M, Sugiura M (1994) The existence of eukaryotic ribonucleoprotein consensus sequence-type RNA-binding proteins in a prokaryote, Synechococcus 6301. Nucleic Acids Res 22:25–31

    CAS  PubMed  Google Scholar 

  10. Khattab A, Pica-Mattoccia L, Klinkert MQ, Wenger R, Cioli D (1998) Cyclosporins: lack of correlation between antischistosomal properties and inhibition of cyclophilin isomerase activity. Exp Parasitol 90:103–109

    CAS  PubMed  Google Scholar 

  11. Anderson M, Fair K, Amero S, Nelson S, Harte PJ, Diaz MO (2002) A new family of cyclophilins with an RNA recognition motif that interact with members of the trx/MLL protein family in Drosophila and human cells. Dev Genes Evol 212:107–113

    CAS  PubMed  Google Scholar 

  12. Shieh BH, Stamnes MA, Seavello S, Harris GL, Zuker CS (1989) The ninaA gene required for visual transduction in Drosophila encodes a homologue of cyclosporin A-binding protein. Nature 338:67–70

    CAS  PubMed  Google Scholar 

  13. Schreiber SL, Crabtree GR (1992) The mechanism of action of cyclosporin A and FK506. Immunol Today 13:136–142

    Article  CAS  PubMed  Google Scholar 

  14. Franke EK, Luban J (1995) Cyclophilin and gag in HIV-1 replication and pathogenesis. Adv Exp Med Biol 374:217–228

    CAS  PubMed  Google Scholar 

  15. Montague JW, Hughes FM Jr, Cidlowski JA (1997) Native recombinant cyclophilins A, B, and C degrade DNA independently of peptidylprolyl cis-trans-isomerase activity. Potential roles of cyclophilins in apoptosis. J Biol Chem 272:6677–6684

    CAS  PubMed  Google Scholar 

  16. Rycyzyn MA, Clevenger CV (2002) The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer. Proc Natl Acad Sci U S A 99:6790–6795

    CAS  PubMed  Google Scholar 

  17. Hoffmann K, Handschumacher RE (1995) Cyclophilin-40: evidence for a dimeric complex with hsp90. Biochem J 307:5–8

    CAS  PubMed  Google Scholar 

  18. Crompton M, Ellinger H, Costi A (1988) Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress. Biochem J 255:357–360

    CAS  PubMed  Google Scholar 

  19. Kenan DJ, Query CC, Keene JD (1991) RNA recognition: towards identifying determinants of specificity. Trends Biochem Sci 16:214–220

    CAS  PubMed  Google Scholar 

  20. Zeng L, Zhou Z, Xu J, Zhao W, Wang W, Huang Y, Cheng C, Xu M, Xie Y, Mao Y (2001) Molecular cloning, structure and expression of a novel nuclear RNA-binding cyclophilin-like gene (PPIL4) from human fetal brain. Cytogenet Cell Genet 95:43–47

    CAS  PubMed  Google Scholar 

  21. Krzywicka A, Beisson J, Keller AM, Cohen J, Jerka-Dziadosz M, Klotz C (2001) KIN241: a gene involved in cell morphogenesis in Paramecium tetraurelia reveals a novel protein family of cyclophilin-RNA interacting proteins (CRIPs) conserved from fission yeast to man. Mol Microbiol 42:257–267

    CAS  PubMed  Google Scholar 

  22. Zorio DA, Blumenthal T (1999) U2AF35 is encoded by an essential gene clustered in an operon with RRM/cyclophilin in Caenorhabditis elegans. RNA 5:487–494

    CAS  PubMed  Google Scholar 

  23. Teigelkamp S, Achsel T, Mundt C, Gothel SF, Cronshagen U, Lane WS, Marahiel M, Luhrmann R (1998) The 20 kD protein of human [U4/U6.U5] tri-snRNPs is a novel cyclophilin that forms a complex with the U4/U6-specific 60 kD and 90 kD proteins. RNA 4:127–141

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cristiana Valle.

Additional information

P Note: The nucleotide sequence reported in this paper is available in the GenBankTM database under the accession number: AY754868

Rights and permissions

Reprints and permissions

About this article

Cite this article

Valle, C., Troiani, A.R., Lazzaretti, P. et al. Molecular and biochemical characterization of a protein cyclophilin from the nematode Haemonchus contortusP . Parasitol Res 96, 199–205 (2005). https://doi.org/10.1007/s00436-005-1329-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-005-1329-3

Keywords

Navigation