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

Nat Commun. 2021 Jun 18;12(1):3788. doi: 10.1038/s41467-021-24083-y.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport / physiology
  • Cell Membrane / parasitology*
  • Cells, Cultured
  • Host-Parasite Interactions
  • Humans
  • Protozoan Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Secretory Pathway / physiology
  • Toxoplasma / metabolism*
  • Toxoplasmosis / pathology*
  • Virulence Factors

Substances

  • Protozoan Proteins
  • Virulence Factors
  • RON protein
  • Receptor Protein-Tyrosine Kinases