ATPase7

ATPase7 (PF3D7_0319000) is a P4-type ATPase phospholipid flippase that operates at the ookinete plasma membrane to enable Plasmodium transmission through the mosquito midgut (PMID:34301597). In P. yoelii, ATPase7 localizes to the ookinete plasma membrane, forms a complex with the flippase cofactor CDC50C, and drives inward translocation of phosphatidylcholine across the bilayer (PMID:34301597). This flippase activity is specifically required for ookinete survival during traversal of the midgut epithelium: parasites lacking ATPase7 invade the midgut but are eliminated within epithelial cells by a complement-independent mechanism, and microinjecting depleted ookinetes directly into the hemocoel bypasses the block and restores transmission (PMID:34301597). Consistent with an essential role, the P. berghei ortholog is refractory to gene deletion (PMID:26796412). Beyond these findings, no further mechanistic detail for ATPase7 has been characterized in the available corpus.

1. 2016 Medium

   Whether ATPase7 is dispensable was unknown; a systematic deletion screen established that it is essential and provisionally a lipid transporter.

   Evidence Genome-wide genetic screen of transporters with attempted gene deletion in P. berghei

   PMID:26796412

   Open questions at the time

   • Refractoriness to deletion does not identify the essential stage or the molecular activity
   • No localization, substrate, or partner defined
   • Aminophospholipid transporter classification was inferred, not demonstrated
2. 2021 High

   The molecular activity and stage-specific requirement were unknown; multiple orthogonal experiments established ATPase7 as a CDC50C-partnered phosphatidylcholine flippase at the ookinete plasma membrane required for surviving midgut epithelium traversal.

   Evidence Gene knockout, live fluorescence localization, co-immunoprecipitation with CDC50C, phospholipid uptake assay, and hemocoel microinjection rescue in P. yoelii

   PMID:34301597

   Open questions at the time

   • Structural basis of ATP-driven phospholipid translocation not resolved
   • How loss of PC flipping triggers ookinete elimination within epithelial cells is undefined
   • Whether functions are conserved in the human parasite P. falciparum (PF3D7_0319000 itself) not directly tested

• It remains unknown whether ATPase7 has functions in blood-stage or other life-cycle stages beyond the ookinete, and what structural features couple ATP hydrolysis to phospholipid transport.
• No blood-stage functional data in the corpus
• No structural or catalytic mechanism characterized
• No direct characterization of the P. falciparum PF3D7_0319000 protein