Affinage · Toxoplasma gondii

GRA60

putative transmembrane protein · UniProt S8GNA6

Annotated
2026-09-08
1 papers in source corpus 1 papers cited in narrative 5 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRA60 is a Toxoplasma gondii dense granule effector that protects the intracellular parasite from host cell-autonomous immunity (PMID:33040458). In the type I RH strain, GRA60 localizes to the vacuolar space and the parasitophorous vacuolar membrane (PVM) (PMID:33040458), where it functions to block recruitment of host immunity-related GTPases Irgb10 and Irga6 to the PVM: deletion of GRA60 permits IRG loading onto the vacuole (PMID:33040458) and reduces parasite virulence in mice (PMID:33040458). Epistasis analysis places GRA60 in the same IRG-resistance pathway as ROP5 rather than acting additively (PMID:33040458), and GRA60 physically associates with the virulence kinase ROP18 (PMID:33040458), indicating it operates within the ROP5/ROP18 virulence-effector machinery at the PVM. Beyond this genetic and localization framework in the RH strain, the biochemical mechanism by which GRA60 acts within the complex has not been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2020 Medium

    Establishing where GRA60 resides was the first step in assigning it a role; localization to the vacuolar space and PVM placed it at the host-parasite interface where immune effectors are engaged.

    Evidence Direct localization of the dense granule protein by microscopy/fractionation in RH strain

    PMID:33040458

    Open questions at the time
    • Does not define how GRA60 is trafficked to or retained at the PVM
    • No topology or membrane-association mechanism established
  2. 2020 Medium

    Whether GRA60 mattered for pathogenesis was tested by knockout, showing it is required for full virulence and thereby linking the protein to a functional in vivo role.

    Evidence Gene knockout in RH strain with in vivo mouse virulence assay

    PMID:33040458

    Open questions at the time
    • Does not distinguish direct immune-evasion contribution from other pathways
    • Single strain background tested
  3. 2020 Medium

    The molecular basis of the virulence defect was pinpointed by showing GRA60 loss permits Irgb10 and Irga6 recruitment to the PVM, establishing GRA60 as an inhibitor of IRG-mediated host defense.

    Evidence Knockout combined with immunofluorescence monitoring IRG recruitment to the PVM in RH strain

    PMID:33040458

    Open questions at the time
    • Mechanism of IRG exclusion (direct blocking vs. modification) unknown
    • Does not address other IRG or GBP family members
  4. 2020 Low

    To locate GRA60 within known virulence machinery, epistasis and association were tested, placing it in the same pathway as ROP5 and physically linking it to the ROP18 kinase.

    Evidence Double-knockout epistasis (RHΔgra60Δrop5) with IRG readout, plus Co-IP association of GRA60 with ROP18

    PMID:33040458

    Open questions at the time
    • ROP18 association is a single Co-IP without reciprocal validation
    • Whether GRA60 is a ROP18 substrate, regulator, or scaffold is undetermined
    • Stoichiometry and architecture of the GRA60-ROP5-ROP18 complex unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The biochemical function of GRA60 within the ROP5/ROP18 complex and whether its role is conserved beyond the type I RH strain remain open.
  • No structural or enzymatic activity defined for GRA60
  • No characterization in type II or III strains
  • Direct molecular interaction of GRA60 with IRGs untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
ROP18ROP5 (SAME GENETIC PATHWAY)
Complex memberships
ROP5/ROP18-containing virulence effector complex

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 GRA60 is a dense granule protein that localizes to the vacuolar space and parasitophorous vacuolar membrane (PVM) in Toxoplasma gondii type I RH strain. Direct localization experiment (microscopy/fractionation of dense granule protein) Cellular microbiology Medium 33040458
2020 GRA60 contributes to virulence in mice; deletion of GRA60 from the RH strain results in reduced virulence, establishing a functional role in pathogenesis. Loss-of-function (gene knockout) with in vivo virulence assay in mice Cellular microbiology Medium 33040458
2020 Deletion of GRA60 in the RH strain leads to recruitment of host IRG family members Irgb10 and Irga6 to the PVM, demonstrating that GRA60 normally inhibits IRG-mediated host defense at the PVM. Loss-of-function (gene knockout) with immunofluorescence microscopy monitoring IRG recruitment to the PVM Cellular microbiology Medium 33040458
2020 Epistasis analysis shows that deletion of GRA60 in an RHΔrop5 background results in IRG recruitment comparable to either single knockout alone, indicating GRA60 and ROP5 operate in the same pathway/complex for IRG resistance rather than additively. Genetic epistasis (double-knockout construction RHΔgra60Δrop5 vs. single knockouts, with IRG recruitment assay) Cellular microbiology Medium 33040458
2020 GRA60 is found physically associated with ROP18, a serine-threonine kinase component of the virulence complex, suggesting GRA60 functions as part of the ROP18-containing effector complex that inhibits IRG-mediated host immunity. Co-immunoprecipitation / association assay (GRA60 found associated with ROP18) Cellular microbiology Low 33040458

Source papers

Stage 0 corpus · 1 paper · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Toxoplasma gondii GRA60 is an effector protein that modulates host cell autonomous immunity and contributes to virulence. Cellular microbiology 24 33040458