PfJ23

PfJ23 (PF3D7_1001900) is a mostly α-helical exported protein of Plasmodium falciparum that functions as a molecular scaffold linking Maurer's cleft machinery to the virulence factor PfEMP1 (PMID:30576479). Recombinant PfJ23 adopts different oligomeric forms under reducing versus non-reducing conditions, indicating redox-sensitive self-association (PMID:30576479). It binds directly to the Maurer's cleft marker PfSBP1 (skeleton binding protein 1) and to the cytoplasmic tail of PfEMP1, and partially co-localizes with each during intraerythrocytic development (PMID:30576479). Because PfSBP1 and the PfEMP1 cytoplasmic tail can engage PfJ23 simultaneously to form a trimeric complex in vitro, PfJ23 harbors distinct, non-overlapping binding sites for the two partners, positioning it as a bridging component in the trafficking of PEXEL-negative surface proteins to the infected erythrocyte membrane (PMID:30576479). Beyond this in vitro interaction and localization evidence, the cellular consequences of PfJ23 function — including any loss-of-function phenotype — have not been characterized in the available corpus.

1. 2018 Medium

   Establishing the physical nature of PfJ23 answered whether the uncharacterized exported protein has a defined fold and quaternary behavior that could support a structural/scaffolding role.

   Evidence In vitro biochemical characterization and in silico secondary structure prediction of recombinant PfJ23

   PMID:30576479

   Open questions at the time

   • No experimental high-resolution structure; secondary structure is predicted in silico
   • Physiological relevance of the redox-dependent oligomeric states in the parasite is untested
   • No mapping of which residues drive self-association
2. 2018 Medium

   Identifying PfSBP1 and the PfEMP1 cytoplasmic tail as direct binding partners placed PfJ23 within the PEXEL-negative protein export pathway rather than leaving it functionally orphan.

   Evidence Direct pulldown/binding assays with purified recombinant and native PfJ23 plus immunofluorescence co-localization in infected erythrocytes

   PMID:30576479

   Open questions at the time

   • Co-localization is only partial, so the interaction may occur in a defined subcompartment or transiently
   • Binding sites on PfJ23 for each partner are not mapped at residue level
   • No demonstration that these interactions occur at endogenous stoichiometry in vivo
3. 2018 Medium

   Demonstrating simultaneous binding of both partners answered whether PfJ23 could act as a bridging scaffold, showing it can nucleate a trimeric complex with distinct sites for each partner.

   Evidence In vitro ternary complex reconstitution assay with purified recombinant proteins

   PMID:30576479

   Open questions at the time

   • Ternary complex shown only in vitro with recombinant proteins; not reconstituted or validated in the parasite
   • Functional consequence of complex formation for PfEMP1 trafficking or surface presentation is untested
   • Whether complex assembly is regulated (e.g. by redox state or oligomerization) is unknown

• It remains unknown whether PfJ23 is functionally required for PfEMP1 export, cytoadherence, or parasite virulence in vivo.
• No loss-of-function genetics for PfJ23
• No demonstration that PfJ23 is required for PfEMP1 surface display or cytoadherence
• No structural map of the two binding interfaces