Role of two histone-fold domain proteins in Plasmodium parasites

Abstract

Malaria is caused by Plasmodium parasites (phylum Apicomplexa) and together with AIDS and tuberculosis is still one of the most deadly infectious diseases in the poorest areas of the world. The difficulty to control the mosquito, the lack of an effective vaccine and development of drug resistance make the identification of new potential drug/vaccine targets a priority for the design of intervention strategies. In Plasmodium parasites two proteins have been annotated containing two histone-fold domain (HFD), DNA binding domain found in histones and transcription factors, NF-YB and NF-YC subunits. In P.falciparum, this protein is distributed in the cytoplasm in all stages of the intraerythrocytic cycle, but it is also present in the nucleus of trophozoite and schizont. Probably the HFD is involved in different functions during the life cycle. In P. berghei we named NF-Yb and Yc as Oocyst Rupture Proteins (ORP1 and ORP2) due to the phenotype of knock-out mutants. Moreover, the HFDs detected in ORP1 and 2 may interact leading to the rupture of the oocyst and parasite transmission in P. berghei. The present knowledge of the ORPs/PfNF-YB/YC thus suggests that the proteins carry out different functions in asexual blood stages and in the oocyst. The aim of this project is to further elucidate the roles of these proteins. We intend to approach the experiments using molecular and cellular biology, biochemistry and advanced microscopy. Proteomic and bioinformatics approaches will be fundamental to identify interactor factors. Finally, the elucidation of the interaction of NF-YB/DNA in P. falciparum and possible dimerization NY-YB/C in P. berghei will give new and innovative information in protein/DNA interactions. (AU)