Abstract
Eukaryotic Armadillo (ARM) repeat proteins are multifaceted with prominent roles in cell-cell adhesion, cytoskeletal regulation and intracellular signaling among many others. One such ARM repeat containing protein, ARM Repeats Only (ARO), has recently been demonstrated in both Toxoplasma (TgARO) and Plasmodium (PfARO) parasites to be targeted to the rhoptries during the late asexual stages. TgARO has been implicated to play an important role in rhoptry positioning i.e. directing the rhoptry towards the apical end of the parasite. Here, we report for the first time that PfARO exhibits a DNA binding property and a dynamic sub-cellular localization between the nucleus (early schizont) and rhoptry (late schizont) during the different stages of the asexual blood-stage life cycle. PfARO possesses a putative nuclear export signal (NES) and the nucleo-apical shuttling was sensitive to Leptomycin B (LMB) suggesting that the nuclear export was mediated by CRM1. Importantly, PfARO specifically bound an A-T rich DNA sequence of the P. falciparum Gyrase A (PfgyrA) gene, suggesting that the DNA binding specificity of PfARO is likely due to the AT-richness of the probe. This is a novel functional characteristic that has not been reported previously for any P. falciparum ARM containing protein and suggests a putative role for PfARO in gene regulation. This study describes for the first time a conserved P. falciparum ARM repeat protein with a high degree of functional versatility.
Highlights
Apicomplexan parasites are the cause of enormous disease burden worldwide
SDS-PAGE analysis of the purified Recombinant PfARO (rPfARO) protein showed a monomeric protein with an expected mobility of ~32 kDa under reducing conditions while under non-reducing conditions an additional prominent ~60 kDa band was observed suggesting that recombinant P. falciparum ARO (PfARO) has a propensity to undergo cysteine mediated dimerization (Fig 1B)
PfARO protein consists of an odd number of cysteine residues, suggesting that one cysteine may be involved in homo-dimerization
Summary
Apicomplexan parasites are the cause of enormous disease burden worldwide. The phylum Apicomplexa consists of numerous pathogenic protozoans such as Plasmodium falciparum, Toxoplasma gondii, Theileria annulata and Neospora caninum, which cause various diseases in both humans and a variety of economically important animal species. The human malaria parasite P. falciparum is an obligate intracellular protozoan with a complex lifecycle and a leading cause of malaria mortality reflected in around a million deaths annually [1]. Dynamic Localization of Armadillo Domain Protein in P. falciparum
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
