RPP2

TgRPP2 (TgP2) is an acidic ribosomal stalk protein of Toxoplasma gondii that additionally moonlights at the tachyzoite surface, where it participates in host cell invasion (PMID:25280460). Epitope-tagged TgP2 localizes to the surface of free tachyzoites, and — unlike its Plasmodium falciparum ortholog — it does not relocate to the host cell membrane of infected fibroblasts and forms only weak SDS-resistant dimers rather than stable oligomers (PMID:25280460). Antibodies directed against surface TgP2 block tachyzoite invasion, establishing a functional role for the surface-exposed pool in host cell entry (PMID:25280460). Structurally, its ~50-residue C-terminal domain is intrinsically disordered, retaining only short segments with transient secondary-structure propensity, and it exists in a concentration-dependent monomer–multimer equilibrium (PMID:25412900). Beyond invasion, recombinant TgRPP2 binds murine macrophages and modulates their proliferation, apoptosis, phagocytosis, nitric oxide production, and cytokine secretion, pointing to an extracellular immunomodulatory activity (PMID:33917244).

1. 2014 Medium

   It was unknown whether the Toxoplasma ribosomal stalk protein P2 had any extra-ribosomal localization; epitope-tag imaging showed it reaches the free tachyzoite surface, distinguishing it from the host-membrane-targeting Plasmodium ortholog and revealing a moonlighting distribution.

   Evidence Epitope-tagged transfection with live/immunofluorescence localization, plus CD spectroscopy and SDS-PAGE oligomerization assay in T. gondii

   PMID:25280460

   Open questions at the time

   • mechanism of surface trafficking of a ribosomal protein not defined
   • no genetic knockout to test endogenous requirement
   • relationship between the ribosomal and surface pools unquantified
2. 2014 Medium

   Whether surface P2 contributes functionally to infection was open; antibody blockade of invasion demonstrated that the surface-localized protein is required for efficient tachyzoite entry into host cells.

   Evidence Invasion inhibition assay using anti-P2 antibodies in T. gondii

   PMID:25280460

   Open questions at the time

   • host receptor or binding partner mediating invasion not identified
   • antibody blockade does not distinguish direct adhesion from downstream steps
3. 2014 Medium

   The structural basis of the functional C-terminus was unknown; NMR and CD showed it is intrinsically disordered with only transient secondary-structure propensity and a monomer-multimer equilibrium, framing its interactions as those of a flexible domain.

   Evidence NMR (1H-15N HSQC), CD spectroscopy, and gel filtration of the recombinant C-terminal domain

   PMID:25412900

   Open questions at the time

   • no structure of the full-length protein or ribosome-bound form
   • functional consequence of the disorder for invasion not tested
4. 2021 Low

   Whether surface/secreted TgRPP2 acts on host immune cells was unaddressed; recombinant protein bound macrophages and altered their proliferation, apoptosis, phagocytosis, NO output, and cytokines, indicating an extracellular immunomodulatory role.

   Evidence Recombinant TgRPP2 binding and functional assays on murine Ana-1 macrophages in vitro

   PMID:33917244

   Open questions at the time

   • in vitro recombinant protein on a heterologous murine cell line; no parasite genetic manipulation
   • macrophage receptor for TgRPP2 not identified
   • relevance to in vivo infection unestablished

• The molecular partners that link surface TgRPP2 to invasion and to macrophage engagement, and the trafficking route that delivers a ribosomal protein to the tachyzoite surface, remain unknown.
• no host receptor identified for invasion or immunomodulation
• no genetic loss-of-function evidence for the endogenous protein
• surface-targeting mechanism uncharacterized