CX3CL1 binding protein-2 (CBP2) of Plasmodium falciparum binds nucleic acids

Abstract

Several exported Plasmodium falciparum(Pf) proteins contribute to malaria biology through their involvement in cytoadherence, immune evasion and host cell remodelling. Many of these exported proteins and other host molecules are present in iRBC (infected red blood cell) generated extracellular vesicles (EVs), which are responsible for host cell modification and parasite development. CX3CL1 binding proteins (CBPs) present on the surface of iRBC have been reported to contribute to cytoadhesion by binding with the chemokine CX3CL1 via their extracellular domains. Here, we have characterized the cytoplasmic domain of CBP2to understand its function in parasite biology using biochemical and biophysical methods. Recombinant cytoplasmic CBP2 (rcCBP2) binds nucleic acids showing interaction with DNA/RNA. rcCBP2 shows dimer formation under non-reducing conditions highlighting the role of disulphide bonds in oligomerization while ATP binding leads to structural changes in the protein. In vitro interaction studies depict its binding with a Maurers cleft resident protein PfSBP1, which is influenced by ATP binding of rcCBP2. Our results suggest CBP2 as a two-transmembrane (2TM) receptor responsible for targeting EVs and delivering cargo to host endothelial cells. We propose CBP2 as an important molecule having roles in cytoadherence and immune modulation through its extracellular and cytoplasmic domains respectively.