Identification of theLeishmania majorProteinsLmjF07.0430, LmjF07.0440, and LmjF27.2440 asComponents of Fatty Acid Synthase II

[摘要] Leishmania majorcauses leishmaniasis and is grouped within the Trypanosomatidae family, which also includes the etiologic agent for African sleeping sickness,Trypanosoma brucei. Previous studies onT. bruceishowed that acyl carrier protein (ACP) of mitochondrial fatty acid synthase type 2 (FASII) plays a crucial role in parasite survival. Additionally, 3-oxoacyl-ACP synthaseTbKASIII as well asTbHTD2 representing 3-hydroxyacyl-ACP dehydratase were also identified; however, 3-oxoacyl-ACP reductaseTbKAR1 has hitherto evaded positive identification. Here, potentialLeishmaniaFASII components LmjF07.0440 and LmjF07.0430 were revealed as 3-hydroxyacyl-ACP dehydratasesLmHTD2-1 andLmHTD2-2, respectively, whereas LmjF27.2440 was identified asLmKAR1. TheseLeishmaniaproteins were ectopically expressed inSaccharomyces cerevisiae htd2Δoroar1Δrespiratory deficient cells lacking the corresponding mitochondrial FASII enzymes Htd2p and Oar1p. Yeast mutants producing mitochondrially targeted versions of the parasite proteins resembled the self-complemented cells for respiratory growth. This is the first identification of a FASII-like 3-oxoacyl-ACP reductase from a kinetoplastid parasite.

[学科分类] 基础医学