ATPTG2

PF3D7_0611300 (ATPTG2) is a mitochondrial ATP synthase-associated subunit of Plasmodium falciparum, identified as a component of the parasite's ATP synthase complex through epitope tagging and immunolocalization to the mitochondrion (PMID:21984828). Blue native gel electrophoresis of mitochondrial membranes places this complex at greater than 1 MDa, consistent with a dimeric assembly and implying additional, non-canonical subunits beyond the seven canonical ones studied (PMID:21984828). Although disruption of the β and γ subunits was unsuccessful, indicating the complex is essential in blood stages, this essentiality was established for those catalytic subunits and not for ATPTG2 itself (PMID:21984828). Beyond its membership in this mitochondrial ATP synthase complex (PMID:21984828), no specific catalytic or regulatory function has been experimentally established for ATPTG2 in the available corpus.

1. 2011 Medium

   It was unknown whether P. falciparum assembles a canonical mitochondrial ATP synthase and which proteins constitute it; tagging and native gel analysis established that ATPTG2 co-localizes to the mitochondrion within a >1 MDa dimeric complex, placing it among the subunits of the parasite ATP synthase.

   Evidence Epitope tagging with immunolocalization and blue native gel electrophoresis of mitochondrial membranes, plus attempted gene disruption of β and γ subunits, in P. falciparum

   PMID:21984828

   Open questions at the time

   • ATPTG2's individual catalytic or structural role is not distinguished from the complex as a whole
   • Essentiality was tested for the β and γ subunits, not for ATPTG2
   • No stoichiometry, topology, or interaction map for ATPTG2 within the complex
2. 2009 Low

   Whether the membrane-anchor subunits of the Plasmodium ATP synthase are conserved was uncertain; computational and proteomic analysis showed subunit a lacks an essential Arg in transmembrane helix IV, indicating these membrane subunits are divergent from canonical eukaryotic orthologs.

   Evidence Computational structural fingerprint analysis and comparison against proteomics data in Plasmodium spp.

   PMID:19682605

   Open questions at the time

   • Bioinformatic prediction without direct experimental validation, and not specific to ATPTG2
   • Does not establish whether ATPTG2 is one of the divergent membrane subunits
   • No functional consequence of the divergence tested

• The specific molecular contribution of ATPTG2 to ATP synthase assembly, catalysis, or dimerization, and whether ATPTG2 itself is essential, remain unresolved.
• No ATPTG2-specific knockout or knockdown phenotype
• No structural placement of ATPTG2 within the dimeric complex
• No defined biochemical activity for ATPTG2