Characterizing the Function of the Conserved ACDC Domain in Plasmodium falciparum ApiAP2 Proteins

Abstract

Plasmodium falciparum is the cause of the deadliest form of malaria, the most prevalent infectious disease worldwide and one of the most deleterious to personal and national development. Despite the complex life cycle of the parasite and the precise nature of its genetic regulation, only one relatively small family of putative specific transcription factors have been identified in its genome, the ApiAP2 proteins. These proteins span a wide range of sizes, and yet the only functional domain that had been identified in the family was the DNA-binding AP2 domain, of which each protein can contain 1-3 copies. Recently however, a few studies reported the presence of a novel, conserved C-terminal domain of unknown function that shows no homology to any other known domain, the ACDC domain. This study sought to determine the function of this domain, including whether the domain interacts with itself and hence serves to mediate dimerization between ApiAP2 proteins that have it. The results show that the domain might dimerize, and also that it interacts with other, mostly transcription-associated proteins in the parasite. This study has therefore served to lay the groundwork for further characterization of the function of the ACDC domain. Since the domain is not present in humans, understanding its purpose would not only help to elucidate a fundamental part of the parasite's biology, but could also provide an ideal target for powerful therapeutic intervention against the disease, perhaps finally leading to the eradication of this terrible affliction.