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Characterization of the ADP/ATP carrier protein (PF3D7_1004800) in Plasmodium falciparum
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Characterization of the ADP/ATP carrier protein (PF3D7_1004800) in Plasmodium falciparum

Karen Lennie Malanda
Master of Science (M.S.), Drexel University
May 2024
DOI:
https://doi.org/10.17918/00010637
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Abstract

Plasmodium falciparum Carrier proteins
Malaria caused by Plasmodium species particularly Plasmodium falciparum remains a global public health problem. Despite the availability of multiple treatment options, the battle to completely eradicate malaria continues to face numerous challenges. One significant challenge is the parasite's development of resistance to nearly all antimalarials that have been used, including chloroquine and artemisinin. As such, fully understanding the essential pathways of Plasmodium parasites is vital in identifying possible drug targets. One of the possible drug targets is the ADP/ATP carrier protein (PF3D7_1004800) based upon its predicted essentiality in P. falciparum. Literature on various model organisms such as Saccharomyces cerevisiae has provided insights into the function of the ADP/ATP carrier protein in mitochondrial ATP export. Using the CRISPR-Cas9 system coupled with the Dicre recombinase system, a conditional knockout of the P. falciparum ADP/ATP carrier protein was induced. Additionally, the TetR-DOZI aptamer system was also utilized to induce a conditional knockdown of the protein. Here we demonstrate that i) ADP/ATP (PF3D7_1004800) is essential for the survival of the parasite. ii) Knockdown of this protein affects the parasite's mitochondrial membrane potential. The essentiality of this ADP/ATP carrier protein and its sequence divergence from mammalian counterparts lacking the conserved RRRMMM conserved domain suggest that it is a prospective antimalarial drug target.

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