PF3D7_0904000

PF3D7_0904000 (PFI0195c) is a putative GTPase-activating protein whose only functional characterization comes from heterologous expression in Saccharomyces cerevisiae, where it conferred resistance to mefloquine, cycloheximide, and halofantrine, localized to the Golgi complex, and was found upregulated in some P. falciparum strains by RT-PCR (PMID:15664648). Beyond this single yeast-based study, its biochemical GAP activity, its endogenous localization and substrate in P. falciparum, and its in-parasite mechanism have not been characterized in the available corpus.

1. 2005 Low

   To ask whether the uncharacterized PFI0195c contributes to antimalarial drug response, the gene was expressed heterologously and screened for a resistance phenotype, establishing the first functional link between this putative GAP and mefloquine resistance.

   Evidence Yeast expression of a P. falciparum library followed by mefloquine selection, with immunolocalization in yeast and semi-quantitative RT-PCR across P. falciparum strains

   PMID:15664648

   Open questions at the time

   • Single-lab heterologous yeast system; no direct biochemical demonstration of GAP activity
   • Golgi localization was shown in yeast, not in P. falciparum
   • No functional consequence demonstrated in the parasite itself; the specific GTPase substrate is unidentified

• Whether PF3D7_0904000 possesses genuine GAP activity, what small GTPase it acts on, where it localizes in the parasite, and how it mechanistically influences mefloquine response in P. falciparum all remain unresolved.
• No in vitro reconstitution of GAP activity
• No identified GTPase target or interacting partners in the parasite
• No endogenous localization or genetic knockout/knockdown phenotype in P. falciparum