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Structural insights into an atypical secretory pathway kinase crucial for Toxoplasma gondii invasion

Author

Listed:
  • Gaëlle Lentini

    (University of Geneva)

  • Rouaa Ben Chaabene

    (University of Geneva)

  • Oscar Vadas

    (University of Geneva)

  • Chandra Ramakrishnan

    (University of Zurich)

  • Budhaditya Mukherjee

    (University of Geneva
    School of Medical Science and Technology)

  • Ved Mehta

    (Institute of Biochemistry, ETH Zurich)

  • Matteo Lunghi

    (University of Geneva)

  • Jonas Grossmann

    (ETH Zurich and University of Zurich
    The Swiss Institute of Bioinformatics, SIB)

  • Bohumil Maco

    (University of Geneva)

  • Rémy Visentin

    (University of Geneva)

  • Adrian B. Hehl

    (University of Zurich)

  • Volodymyr M. Korkhov

    (Institute of Biochemistry, ETH Zurich
    Paul Scherrer Institute)

  • Dominique Soldati-Favre

    (University of Geneva)

Abstract

Active host cell invasion by the obligate intracellular apicomplexan parasites relies on the formation of a moving junction, which connects parasite and host cell plasma membranes during entry. Invading Toxoplasma gondii tachyzoites secrete their rhoptry content and insert a complex of RON proteins on the cytoplasmic side of the host cell membrane providing an anchor to which the parasite tethers. Here we show that a rhoptry-resident kinase RON13 is a key virulence factor that plays a crucial role in host cell entry. Cryo-EM, kinase assays, phosphoproteomics and cellular analyses reveal that RON13 is a secretory pathway kinase of atypical structure that phosphorylates rhoptry proteins including the components of the RON complex. Ultimately, RON13 kinase activity controls host cell invasion by anchoring the moving junction at the parasite-host cell interface.

Suggested Citation

  • Gaëlle Lentini & Rouaa Ben Chaabene & Oscar Vadas & Chandra Ramakrishnan & Budhaditya Mukherjee & Ved Mehta & Matteo Lunghi & Jonas Grossmann & Bohumil Maco & Rémy Visentin & Adrian B. Hehl & Volodymy, 2021. "Structural insights into an atypical secretory pathway kinase crucial for Toxoplasma gondii invasion," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24083-y
    DOI: 10.1038/s41467-021-24083-y
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    Cited by:

    1. Nicolas Dos Santos Pacheco & Albert Tell i Puig & Amandine Guérin & Matthew Martinez & Bohumil Maco & Nicolò Tosetti & Estefanía Delgado-Betancourt & Matteo Lunghi & Boris Striepen & Yi-Wei Chang & Do, 2024. "Sustained rhoptry docking and discharge requires Toxoplasma gondii intraconoidal microtubule-associated proteins," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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