Parasitology



Analysis of the Trypanosoma cruzi cyclophilin gene family and identification of Cyclosporin A binding proteins


M. POTENZA a1, A. GALAT a2, T. A. MINNING a3, A. M. RUIZ a1, R. DURAN a4, R. L. TARLETON a3, M. MARÍN a5, L. E. FICHERA a1 and J. BÚA a1c1
a1 Instituto Nacional de Parasitología “Dr. M. Fatala Chabén”, A.N.L.I.S. Malbrán, Buenos Aires, Argentina
a2 Departement d'Ingenierie et d'Etudes des Proteines, DSV/CEA, Gif-sur-Yvette Cedex, France
a3 Department of Cellular Biology and Centre for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA
a4 Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
a5 Departamento de Bioquímica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay

Article author query
potenza m   [PubMed][Google Scholar] 
galat a   [PubMed][Google Scholar] 
minning ta   [PubMed][Google Scholar] 
ruiz am   [PubMed][Google Scholar] 
duran r   [PubMed][Google Scholar] 
tarleton rl   [PubMed][Google Scholar] 
marin m   [PubMed][Google Scholar] 
fichera le   [PubMed][Google Scholar] 
bua j   [PubMed][Google Scholar] 

Abstract

The Trypanosoma cruzi cyclophilin gene family comprises 15 paralogues whose nominal masses vary from 19 to 110 kDa, namely TcCyP19, TcCyP20, TcCyP21, TcCyP22, TcCyP24, TcCyP25, TcCyP26, TcCyP28, TcCyP29, TcCyP30, TcCyP34, TcCyP35, TcCyP40, TcCyP42 and TcCyP110. Under the conditions used, only some of the T. cruzi cyclophilin paralogue products could be isolated by affinity chromatography. The 15 paralogues were aligned with 495 cyclophilins from diverse organisms. Analyses of clusters formed by the T. cruzi cyclophilins with others encoded in various genomes revealed that 8 of them (TcCyP19, TcCyP21, TcCyP22, TcCyP24, TcCyP35, TcCyP40, TcCyP42 and TcCyP110) have orthologues in many different genomes whereas the other 7 display less-defined patterns of their sequence attributes and their classification to a specific group of cyclophilin's orthologues remains uncertain. Seven epimastigote cDNA clones encoding cyclophilin isoforms were further studied. These genes were found dispersed throughout the genome of the parasite. Amastigote and trypomastigote mRNAs encoding these 7 genes were also detected. We isolated 4 cyclosporin A-binding proteins in T. cruzi epimastigote extracts, which were identified by mass spectrometry as TcCyP19, TcCyP22, TcCyP28 and TcCyP40. Cyclosporin A-binding to these cyclophilins might be of importance to the mechanism of action of Cyclosporin A and its non-immunosuppressive analogues, whose trypanocidal effects were previously reported, and therefore, of potential interest in the chemotherapy of Chagas' disease.

(Received September 9 2005)
(Revised October 8 2005)
(Accepted October 14 2005)


Key Words: Trypanosoma cruzi; cyclophilin; clustering PPIase paralogues; Cyclosporin A binding proteins.

Correspondence:
c1 Instituto Nacional de Parasitología. Av. Paseo Colón 568 (1063) Buenos Aires, Argentina. Tel: +54 11 4331 4019. Fax: +54 11 4331 7142. E-mail: jacbua@yahoo.com


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