Affinage · Toxoplasma gondii

MYR3

putative transmembrane protein · UniProt S8G4M3

Annotated
2026-09-08
4 papers in source corpus 4 papers cited in narrative 5 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYR3 is a membrane-associated protein of the Toxoplasma gondii parasitophorous vacuole that functions as an essential component of the translocon machinery exporting dense granule (GRA) effectors across the parasitophorous vacuole membrane (PVM) into the host cell (PMID:29357375). Localizing to the PV space and PV membranes, MYR3 stably associates with MYR1, forming a complex at the PVM required for effector translocation (PMID:29357375). This machinery comprises at least eight discrete proteins—MYR1, MYR2, MYR3, MYR4, GRA44, GRA45, ROP17, and ASP5—whose individual loss blocks translocation of GRA effectors such as GRA16 and GRA24 and abrogates downstream host responses including c-Myc and cyclin E1 upregulation (PMID:32075880, PMID:32075881). Effector transit through this complex additionally requires the rhoptry kinase ROP17 acting on the host-cytosolic face of the PVM, placing the MYR3 translocon within a defined export pathway (PMID:31366709). Beyond its role as a translocon component and MYR1 partner, no distinct biochemical activity for MYR3 itself has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2018 High

    Established that MYR3 is a genuine PVM-associated protein whose loss specifically blocks export of a subset of GRA effectors, defining it as a translocation factor rather than a general secretory component.

    Evidence Genetic screen for c-Myc upregulation defects with co-localization imaging, membrane fractionation, and GRA16/GRA24 nuclear export readouts in T. gondii

    PMID:29357375

    Open questions at the time
    • Does not resolve whether MYR3 directly contacts translocating effectors or acts structurally
    • The molecular activity of MYR3 (channel, adaptor, chaperone) is undefined
  2. 2018 Medium

    Showed that MYR3, but not MYR2, physically and stably associates with MYR1, defining a discrete MYR1-MYR3 complex at the PVM as the physical basis of translocation.

    Evidence Co-immunoprecipitation/stable association assay and disulfide-linkage analysis of MYR1 fragments in T. gondii

    PMID:29357375

    Open questions at the time
    • No reciprocal IP or structural validation reported
    • Stoichiometry and architecture of the MYR1-MYR3 interaction unknown
  3. 2019 Medium

    Positioned the MYR3-containing complex within a larger pathway by showing the host-cytosolic-facing rhoptry kinase ROP17 is catalytically required for translocation through the same machinery, implicating phosphorylation on the host side of the PVM.

    Evidence Whole-genome sequencing of translocation-defective mutants, catalytically dead ROP17 mutant and trans-complementation, with GRA translocation assay in T. gondii

    PMID:31366709

    Open questions at the time
    • ROP17 substrate at the translocon not identified
    • Whether ROP17 acts directly on MYR3 is unknown
    • Single-lab epistasis
  4. 2020 High

    Defined the full multi-protein composition of the translocon, establishing MYR3 as one of at least eight interdependent components each required for GRA16 export and host transcriptional responses.

    Evidence Affinity purification of MYR1 (Co-IP/MS) plus individual knockout/knockdown with GRA16 translocation and host c-Myc/cyclin E1 readouts in T. gondii TGGT1

    PMID:32075880

    Open questions at the time
    • Direct MYR3 interactions within the eight-component complex not individually mapped
    • Order of assembly of the translocon unknown
  5. 2020 Medium

    Extended the translocon roster by showing the putative acid phosphatase GRA44 associates with MYR1 and that its loss phenocopies translocon disruption, functionally linking it to the MYR3-containing machinery.

    Evidence Immunoprecipitation and conditional GRA44 knockdown with host c-Myc upregulation assay in T. gondii

    PMID:32075881

    Open questions at the time
    • Direct GRA44-MYR3 contact not demonstrated
    • Role of the GRA44 phosphatase domain in translocation unresolved
    • Single Co-IP

Open questions

Synthesis pass · forward-looking unresolved questions
  • The intrinsic molecular activity of MYR3 within the translocon and the mechanism by which effectors are physically threaded across the PVM remain undefined.
  • No structure of MYR3 or the translocon
  • No demonstrated direct contact between MYR3 and translocating effectors
  • Assembly hierarchy and energetics of translocation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
GRA44MYR1ROP17 (FUNCTIONAL/PATHWAY)
Complex memberships
MYR translocon (MYR1, MYR2, MYR3, MYR4, GRA44, GRA45, ROP17, ASP5)MYR1-MYR3 complex

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 MYR3 is a novel protein that localizes to the parasitophorous vacuole (PV) space and co-localizes with PV membranes and MYR1; it 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 PVM into the host cell. Genetic screen for c-Myc up-regulation defects, co-localization imaging, membrane association assay, loss-of-function mutant analysis with GRA16/GRA24 nuclear export readout PLoS pathogens High 29357375
2018 MYR3, but not MYR2, stably associates with MYR1 (whose N- and C-terminal fragments are disulfide-linked), forming a protein complex at the PVM required for effector translocation. Co-immunoprecipitation / stable association assay; disulfide linkage analysis of MYR1 fragments PLoS pathogens Medium 29357375
2020 MYR3 is one of at least eight discrete proteins required for translocation of dense granule effectors (e.g., GRA16) across the PVM into host cells, as part of a complex that includes MYR1, MYR2, MYR3, ROP17, ASP5, GRA44, GRA45, and MYR4. Affinity purification of MYR1 (Co-IP/MS), knockout/knockdown of individual components with GRA16 translocation and host c-Myc/cyclin E1 upregulation as functional readouts mSphere High 32075880
2019 MYR3 is a component of the GRA translocation machinery at the PVM; ROP17, a rhoptry serine/threonine kinase acting on the host cytosolic side of the PVM, is also required for GRA effector translocation across the same machinery that includes MYR1, MYR2, and MYR3. Whole-genome sequencing of translocation-defective mutants, catalytically dead ROP17 mutant analysis, trans-complementation with ROP17 from co-infecting parasites, GRA translocation assay mSphere Medium 31366709
2020 GRA44, which contains a putative acid phosphatase domain, interacts with MYR1 (and by implication the MYR complex including MYR3) as shown by immunoprecipitation, and conditional knockdown of GRA44 phenocopies disruption of the MYR translocon, blocking host c-Myc upregulation. Immunoprecipitation, conditional knockdown (GRA44), host c-Myc upregulation assay 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