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

Gaëlle Lentini, Rouaa Ben Chaabene, Oscar Vadas, Chandra Ramakrishnan, Budhaditya Mukherjee, Ved Mehta, Matteo Lunghi, Jonas Grossmann, Bohumil Maco, Rémy Visentin, Adrian B. Hehl, Volodymyr M. Korkhov () and Dominique Soldati-Favre ()
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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
Ved Mehta: Institute of Biochemistry, ETH Zurich
Matteo Lunghi: University of Geneva
Jonas Grossmann: ETH Zurich and University of Zurich
Bohumil Maco: University of Geneva
Rémy Visentin: University of Geneva
Adrian B. Hehl: University of Zurich
Volodymyr M. Korkhov: Institute of Biochemistry, ETH Zurich
Dominique Soldati-Favre: University of Geneva

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24083-y

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