Abstract
ATP2, a putative type 4 P-type ATPase, is a phosphatidylinositol-4-phosphate (PI4P)-regulated phospholipid transporter with an interesting potential as an antimalarial drug target due to its conservation across Plasmodium species and its essential role in the life cycle of Plasmodium falciparum. Despite its importance, the exact mechanism of its action and regulation is still not fully understood. In this study we used coarse-grained molecular dynamics (CG-MD) to elucidate the lipid-protein interactions between a heterogeneous lipid membrane containing phosphatidylinositol and Plasmodium chabaudi ATP2 (PcATP2), an ortholog of P. falciparum ATP2. Our study reveals structural information of the lipid fingerprint of ATP2, and provides structural information on the potential phosphatidylinositol allosteric binding site. Moreover, we identified a set of evolutionary conserved residues that may play a key role in the binding and stabilization of lipids in the binding pocket.