Affinage · Toxoplasma gondii

MYR2

putative transmembrane protein · UniProt S8G9L5

Annotated
2026-09-08
4 papers in source corpus 4 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYR2 is a membrane-associated protein secreted into the Toxoplasma gondii parasitophorous vacuole where it functions as an essential component of the translocon machinery that exports dense granule (GRA) effector proteins across the PV membrane into the host cell (PMID:29357375, PMID:31366709). It co-localizes with the PV membrane and MYR1 and is required for translocation of GRA effectors such as GRA16 and GRA24 into the host, consistent with a channel/pore-based translocon mechanism through which unfolded effectors pass (PMID:29357375). MYR2 sits within a large MYR1-containing complex that also includes MYR3, ROP17, GRA44, GRA45, MYR4, GRA54, and PPM3C (PMID:32075880). Unlike MYR3, MYR2 does not stably associate with MYR1, indicating it occupies a distinct structural position within this translocon (PMID:29357375). Beyond its assignment to this export complex and PV membrane localization, the molecular details of MYR2's specific contribution to effector translocation have not been further characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2018 High

    Establishing what machinery moves parasite effectors into the host cell, MYR2 was identified as a PV-secreted, membrane-associated protein essential for translocation of a subset of GRA effectors across the PV membrane.

    Evidence genetic screen for c-Myc upregulation defects, fluorescence co-localization, membrane fractionation, and GRA16/GRA24 export assays in T. gondii

    PMID:29357375

    Open questions at the time
    • Does not resolve whether MYR2 forms the translocation channel itself or a regulatory/scaffolding role
    • No structural model of MYR2 within the complex
  2. 2018 Medium

    Addressing the architecture of the translocon, MYR2 was shown not to stably associate with MYR1 (unlike MYR3), placing it at a distinct position within the complex.

    Evidence co-immunoprecipitation distinguishing stable vs unstable associations in T. gondii

    PMID:29357375

    Open questions at the time
    • Single Co-IP; does not identify MYR2's direct binding partners
    • Distinct structural role inferred but not defined
  3. 2018 Medium

    Testing the transport mechanism, blocking transit with a folded DHFR domain fused to disordered effectors impaired export of other effectors, supporting a translocon/pore model requiring effector unfolding.

    Evidence DHFR-fusion block-of-transport experiment in T. gondii

    PMID:29357375

    Open questions at the time
    • Does not directly attribute the channel/pore to MYR2 specifically
    • Single method, single lab
  4. 2019 High

    Independent confirmation established MYR2 as one of three core components of the PVM effector translocation machinery alongside MYR1 and MYR3.

    Evidence genetic mutant analysis, whole-genome sequencing of translocation-defective mutants, and GRA translocation assays in T. gondii

    PMID:31366709

    Open questions at the time
    • Does not define MYR2's biochemical activity
    • Substrate range beyond tested effectors not fully mapped
  5. 2020 Medium

    Mapping the full translocon revealed MYR2 as a member of an at-least-eight-component MYR1 complex, expanding the known composition of the export machinery.

    Evidence affinity purification of MYR1 with mass spectrometry identifying MYR2, MYR3, ROP17, GRA44, GRA45, MYR4, GRA54, and PPM3C in T. gondii strain TGGT1

    PMID:32075880

    Open questions at the time
    • MYR2-specific interactions not validated by reciprocal pull-down
    • Stoichiometry and spatial arrangement of components unknown
  6. 2020 Medium

    GRA44 was placed as a functional associate of the MYR translocon required for host c-Myc upregulation, extending the complex's functional membership adjacent to MYR2.

    Evidence immunoprecipitation showing GRA44-MYR1 interaction and conditional knockdown of GRA44 with c-Myc readout in T. gondii

    PMID:32075881

    Open questions at the time
    • MYR2 implicated only indirectly via the shared complex
    • Direct MYR2-GRA44 contact not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The specific biochemical activity of MYR2 within the translocon and its direct binding partners and structural placement remain undefined.
  • No structural model of the translocon
  • MYR2's direct interaction partners unidentified
  • Whether MYR2 contributes to pore formation, effector recognition, or scaffolding is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
GRA44GRA45GRA54MYR1 (CO-LOCALIZES; DOES NOT STABLY ASSOCIATE)MYR3MYR4PPM3CROP17
Complex memberships
MYR translocon complex (MYR1, MYR2, MYR3, ROP17, GRA44, GRA45, MYR4, GRA54, PPM3C)

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 MYR2 is secreted into the parasitophorous vacuole (PV) space, co-localizes with PV membranes and MYR1, is membrane-associated (consistent with predicted transmembrane domains), and is essential for translocation of a subset of GRA effectors (including GRA16 and GRA24) across the PV membrane into the host cell. Genetic screen for c-Myc up-regulation defects, fluorescence co-localization, membrane association assay, loss-of-function mutant analysis with GRA16/GRA24 export readout PLoS pathogens High 29357375
2018 MYR2 does not stably associate with MYR1 (unlike MYR3, which does stably associate with MYR1), indicating MYR2 occupies a distinct position within the PVM translocon complex. Co-immunoprecipitation / protein interaction assay distinguishing stable vs. unstable associations PLoS pathogens Medium 29357375
2018 Fusing intrinsically disordered GRA effectors to a structured DHFR domain blocks transport of other effectors, consistent with a translocon-based (channel/pore) model of effector transport through the MYR complex. DHFR-fusion block-of-transport experiment as mechanistic test of translocon model PLoS pathogens Medium 29357375
2019 MYR2 is confirmed as one of the three core components of the GRA effector translocation machinery at the PVM, alongside MYR1 and MYR3, and is required for translocation of dense granule effectors across the PVM. Genetic mutant analysis, whole-genome sequencing of translocation-defective mutants, GRA translocation assays mSphere High 31366709
2020 MYR2 is part of a larger MYR1-containing protein complex at the PV; affinity purification of MYR1 co-purifies MYR2 along with MYR3, ROP17, GRA44, GRA45, MYR4, GRA54, and PPM3C, revealing MYR2's placement within an at-least-eight-component translocation complex. Affinity purification / co-immunoprecipitation of MYR1 followed by mass spectrometry identification of interacting proteins mSphere Medium 32075880
2020 GRA44 interacts with the MYR translocon complex (including MYR1, and by extension MYR2 and MYR3) and is required for host cell c-Myc upregulation, placing GRA44 as a functional component associated with the MYR2/MYR1/MYR3 translocon. Immunoprecipitation showing GRA44–MYR1 interaction; conditional knockdown of GRA44 with c-Myc upregulation readout mSphere Medium 32075881

Source papers

Stage 0 corpus · 4 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Identification of a novel protein complex essential for effector translocation across the parasitophorous vacuole membrane of Toxoplasma gondii. PLoS pathogens 75 29357375
2020 Coimmunoprecipitation with MYR1 Identifies Three Additional Proteins within the Toxoplasma gondii Parasitophorous Vacuole Required for Translocation of Dense Granule Effectors into Host Cells. mSphere 53 32075880
2019 Translocation of Dense Granule Effectors across the Parasitophorous Vacuole Membrane in Toxoplasma-Infected Cells Requires the Activity of ROP17, a Rhoptry Protein Kinase. mSphere 50 31366709
2020 The Secreted Acid Phosphatase Domain-Containing GRA44 from Toxoplasma gondii Is Required for c-Myc Induction in Infected Cells. mSphere 23 32075881