FUNCTIONAL CHARACTERIZATION OF ATYPICAL THIOREDOXINS FROM Entamoeba histolytica

ARIAS, DIEGO G.; BIROCCO, FRANCO; SASONI, NATALIA; GUERRERO, SERGIO A.; IGLESIAS, ALBERTO A.

Paraná

Congreso; LIV Annual meeting Argentina Society for Biochemistry and Molecular Biology; 2018

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular y Pan-American Association for Biochemistry and Molecular Biology

Entamoeba histolytica, a unicellular parasite, usually lives and multiplies within the human gut, under reduced oxygen pressure. During tissueinvasion, it is exposed to increased amounts of reactive oxygen species, which are highly toxic for the parasite. The metabolic pathways used bythis organism to cope with such environmental changes and redox homeostasis are a matter of our work. Recently, we characterized in E.histolytica its functional thioredoxins system, composed by thioredoxins (TRXs) and thioredoxin reductase (TRXR). In this work, we present thefunctional characterization of three atypical TRX from E. histolytica (EhTRX111, EhTRX212 and EhTRX289). EhTRX111 (a tail-anchorprotein) and EhTRX289, but not EhTRX212, were able to in vitro reduction (via EhTRXR) of cystine, CySNO, insulin and Eh2CysPrx.However, EhTRX212 was able to coordinate iron-sulfur cluster (ISC) by an in vitroreconstitution assay. By gel filtration chromatography andUV-Vis spectroscopy experiments were detected EhTRX212-ISC complexes. In other hands, we observed the nitrosationCySNO-dependentof EhTRXs. This redox modification generated a partially reversible inactivation of the disulfide reductase activity of these proteins. Thissuggests that this modification could act as a possible regulation of their activity. This work strongly supports the occurrence in E. histolytica ofnew TRXs, which were not previously described in the parasite. Our results extend the knowledge regarding to EhTRX function and suggest thatthese proteins have important functions in redox and iron metabolism of this pathogen parasite. Granted by ANPCyT (PICT2014-2103 andPICT2016-1778).