Affinage · Toxoplasma gondii

TGME49_243250

myosin H · UniProt A0A125YQD4

Annotated
2026-09-10
4 papers in source corpus 4 papers cited in narrative 4 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MyoH (TGME49_243250) is a conoid-anchored motor that powers the first step of the mechanical cascade driving Toxoplasma gondii gliding motility, host-cell invasion, and egress (PMID:26760042). It is tethered to the conoid through three alpha-tubulin suppressor (ATS) domains in its tail, with the tail facing the interior of the conoid barrel and the motor head projecting radially to the exterior of the apical complex (PMID:26760042, PMID:42094507). MyoH drives conoid extrusion using F-actin generated by Formin1 at the preconoidal rings, and this extrusion directs actin flux into the pellicular space to gate assembly of the MyoA glideosome—positioning MyoH upstream of MyoA in force generation and translocating the circular junction from the parasite tip to the apical position where the IMC begins (PMID:26760042, PMID:36109645). Its stable conoid localization is coupled to associated calmodulin-like light chains: MyoH co-localizes with CaM1–CaM3 and its light chain MLC7, and its loss causes CaM3 degradation and CaM1/CaM2 redistribution, indicating MyoH is required for their conoid association (PMID:28475612).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2016 High

    Established that MyoH is a distinct conoid-anchored motor essential for the initiating step of force generation, resolving how motility begins upstream of the known MyoA glideosome.

    Evidence Conditional TetO disruption with domain-deletion mapping and live imaging of motility, invasion, egress, and junction translocation in T. gondii

    PMID:26760042

    Open questions at the time
    • Direct force measurement of MyoH motor activity not performed
    • Actin substrate for MyoH not identified in this study
    • Mechanism of ATS-domain conoid anchoring not resolved structurally
  2. 2017 Medium

    Addressed which light chains stabilize MyoH by showing calmodulin-like proteins associate with and depend on MyoH for conoid localization.

    Evidence Super-resolution microscopy, BirA proximity biotinylation, and AID knockdown of MyoH in T. gondii

    PMID:28475612

    Open questions at the time
    • Interaction inferred from proximity labeling, not confirmed by co-IP/pulldown
    • Functional consequence of each CaM for MyoH motor activity not dissected
    • Stoichiometry of CaM/MLC7 binding to MyoH unknown
  3. 2022 Medium

    Placed MyoH in a mechanistic pathway by linking Formin1-generated F-actin to conoid extrusion and downstream MyoA-glideosome gating.

    Evidence U-ExM and conditional knockdown of preconoidal ring components and Formin1 with imaging of conoid extrusion and actin dynamics in T. gondii

    PMID:36109645

    Open questions at the time
    • MyoH role inferred from pathway context rather than direct MyoH manipulation in this study
    • Quantitative contribution of MyoH versus other factors to extrusion force not measured
    • Regulation coupling extrusion to actin flux not defined
  4. 2026 Medium

    Resolved the spatial orientation of MyoH within the apical complex, showing tail-interior/head-exterior topology consistent with an outward-projecting motor.

    Evidence 3D single-molecule localization microscopy of N- and C-terminally labeled MyoH with two-color tubulin imaging in fixed/gel-expanded parasites (preprint)

    PMID:42094507

    Open questions at the time
    • Preprint, not peer-reviewed
    • Single lab
    • Does not resolve how head orientation couples to F-actin engagement during extrusion

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
CAM1CAM2CAM3FORMIN1 (FUNCTIONAL/PATHWAY LINK)MLC7MYOA (DOWNSTREAM RELAY)
Complex memberships
MyoH–CaM1/CaM2/CaM3–MLC7 conoid motor complex (inferred from proximity labeling)

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 MyoH (TGME49_243250) is anchored to the conoid via three alpha-tubulin suppressor (ATS) domains located in its tail; conditional disruption of TgMyoH severely compromises parasite motility, invasion, and egress, and MyoH is required for translocation of the circular junction from the parasite tip to the apical position where the IMC starts, establishing the first step of force generation along the conoid before relay by MyoA. Conditional gene disruption (TetO system), domain-deletion constructs, live imaging of gliding/invasion/egress, immunofluorescence assay PLoS pathogens High 26760042
2017 Calmodulin-like proteins CaM1, CaM2, and CaM3 co-localize with MyoH (TGME49_243250) at the conoid; proximity biotinylation (BirA fusions to the CaMs) labels MyoH and its light chain MLC7, suggesting physical association; disruption of MyoH leads to degradation of CaM3 or redistribution of CaM1/CaM2, indicating MyoH is required for stable conoid association of these CaMs. Super-resolution microscopy (localization), BirA proximity biotinylation, auxin-induced degron (AID) knockdown of MyoH, immunofluorescence PLoS pathogens Medium 28475612
2022 MyoH (TGME49_243250) uses F-actin produced by Formin1 at the preconoidal rings to generate the mechanical force for conoid extrusion; conoid extrusion in turn directs F-actin flux to the pellicular space, thereby controlling the assembly of the MyoA-glideosome and gating parasite motility. Ultrastructure expansion microscopy (U-ExM), conditional knockdown/disruption of preconoidal ring components and Formin1, live and fixed imaging of conoid extrusion and actin dynamics Nature microbiology Medium 36109645
2026 3D single-molecule super-resolution microscopy (SMLM) of N- and C-terminally labeled MyoH (TGME49_243250) in fixed parasites established that the motor head is radially exterior to the tail within the apical complex, and that the tail faces the interior of the conoid barrel while the motor head faces the exterior. 3D single-molecule localization microscopy (PALM/STORM) in fixed and gel-expanded parasites, two-color imaging with tubulin bioRxivpreprint Medium 42094507

Source papers

Stage 0 corpus · 4 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii. PLoS pathogens 84 28475612
2016 The Conoid Associated Motor MyoH Is Indispensable for Toxoplasma gondii Entry and Exit from Host Cells. PLoS pathogens 75 26760042
2022 Conoid extrusion regulates glideosome assembly to control motility and invasion in Apicomplexa. Nature microbiology 37 36109645
2026 Organization of Myosin H in the Apical Complex of Toxoplasma Gondii Revealed by 3D Single-Molecule Super-Resolution Microscopy. bioRxiv : the preprint server for biology 0 42094507