PF3D7_1023100

PF3D7_1023100 is a putative dynein heavy chain implicated in microtubule-based intracellular transport during Plasmodium morphogenesis. The direct evidence for its cellular role derives from its P. yoelii ortholog DHC3, which localizes to subpellicular microtubules throughout ookinete development and, when disrupted, produces defective ookinete shape, gliding, and apical organelle formation with consequent failure of mosquito infection; at these microtubules DHC3 engages Rab11A and Rab11B in a DHC3-dependent manner, positioning these Rab GTPases as cargo receptors for a subpellicular microtubule-dynein transport motor (PMID:39366980). In P. falciparum, the protein itself is subject to covalent modification by 4-hydroxynonenal upon peroxide-antimalarial-induced oxidative stress, with specific 4-HNE adduct sites mapped by mass spectrometry (PMID:26459031). Beyond these findings, the enzymology, structure, and native complex composition of the P. falciparum protein have not been characterized in the available corpus, and the P. falciparum functional role rests on inference from the P. yoelii ortholog.

1. 2015 Low

   The question of whether the P. falciparum dynein heavy chain is a molecular target of peroxide-based antimalarials was addressed by showing it is covalently modified by a lipid peroxidation product, linking it to oxidative drug action.

   Evidence Mass spectrometry identification of 4-HNE protein conjugates and adduct sites in plakortin-treated P. falciparum

   PMID:26459031

   Open questions at the time

   • Single MS identification of a covalent adduct with no functional follow-up on the dynein heavy chain specifically
   • Whether 4-HNE modification alters motor activity or contributes to drug killing is untested
   • No structural or biochemical characterization of the protein accompanies the adduct mapping
2. 2024 Medium

   The cellular function of the dynein heavy chain was resolved in the P. yoelii ortholog DHC3, establishing it as a subpellicular microtubule motor that transports Rab11-associated cargo required for apical organelle assembly and ookinete morphogenesis.

   Evidence Genetic knockout, fluorescence localization, co-immunoprecipitation, and phenotypic analysis of ookinete morphogenesis and mosquito infection in P. yoelii

   PMID:39366980

   Open questions at the time

   • Findings are in the P. yoelii ortholog DHC3; the exact orthology to P. falciparum PF3D7_1023100 is not explicitly confirmed
   • Motor activity and directionality were not reconstituted biochemically
   • The identity of the transported cargoes downstream of Rab11A/B receptors is not defined

• Whether the P. falciparum protein itself performs the subpellicular microtubule transport function inferred from P. yoelii DHC3, and how its 4-HNE modification relates to that function, remains unresolved.
• No P. falciparum knockout or localization data for PF3D7_1023100
• No structural model or reconstituted motor activity
• No demonstration that the 4-HNE-modified protein is the same functional entity as the P. yoelii ortholog