TAILIEUCHUNG - Báo cáo khoa học: Leishmania infantum LeIF protein is an ATP-dependent RNA helicase and an eIF4A-like factor that inhibits translation in yeast

LeIF, aLeishmaniaprotein similar to the eukaryotic initiation factor eIF4A, which is a prototype of the DEAD box protein family, was origin-ally described as a Th1-type natural adjuvant and as an antigen that indu-ces an IL12-mediated Th1 response in the peripheral blood mononuclear cells of leishmaniasis patients. | ễFEBS Journal Leishmania infantum LeIF protein is an ATP-dependent RNA helicase and an eIF4A-like factor that inhibits translation in yeast Mourad Barhoumi1 N. K. Tanner2 Josette Banroques2 3 Patrick Linder2 and Ikram Guizani1 1 Laboratoire d Epidemiologie et d Ecologie Parasitaire Institut Pasteur de Tunis Tunisia 2 Departement de Microbiologie et Medicine Moleculaire Centre MedicalUniversitaire Geneve Switzerland 3 Centre de Genetique Moleculaire CNRS Gif-sur-Yvette France Keywords ATPase DEAD box eIF4AIII Leishmaniasis unwindase Correspondence I. Guizani Laboratoire d Epidemiologie et d Ecologie Parasitaire Institut Pasteur de Tunis 13 Place Pasteur BP74 1002 Tunis Tunisia Fax 216 71 791 833 Tel 216 71 844 171 E-mail Received 7 July 2006 revised 15 September 2006 accepted 18 September 2006 doi LeIF a Leishmania protein similar to the eukaryotic initiation factor eIF4A which is a prototype of the DEAD box protein family was originally described as a Th1-type natural adjuvant and as an antigen that induces an IL12-mediated Th1 response in the peripheral blood mononuclear cells of leishmaniasis patients. This study aims to characterize this protein by comparative biochemical and genetic analysis with eIF4A in order to assess its potential as a target for drug development. We show that a His-tagged recombinant LeIF protein of Leishmania infantum which was purified from Escherichia coli is both an RNA-dependent ATPase and an ATP-dependent RNA helicase in vitro as described previously for other members of the DEAD box helicase protein family. In vivo experiments show that the LelF gene cannot complement the deletion of the essential TIF1 and TIF2 genes in the yeast Saccharomyces cerevisiae that encode eIF4A. In contrast expression of LeIF inhibits yeast growth when endogenous eIF4A is expressed off only one of its two encoding genes. Furthermore in vitro binding assays show that LeIF interacts with yeast .

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