Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP

Klug, Dennis; Goellner, Sarah; Kehrer, Jessica; Sattler, Julia; Strauss, Leanne; Singer, Mirko; Lu, Chafen; Springer, Timothy A. und Frischknecht, Friedrich (2020): Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP. In: eLife, Bd. 9, e57572

Abstract

Inserted (I) domains function as ligand-binding domains in adhesins that support cell adhesion and migration in many eukaryotic phyla. These adhesins include integrin alpha beta heterodimers in metazoans and single subunit transmembrane proteins in apicomplexans such as TRAP in Plasmodium and MIC2 in Toxoplasma. Here we show that the I domain of TRAP is essential for sporozoite gliding motility, mosquito salivary gland invasion and mouse infection. Its replacement with the I domain from Toxoplasma MIC2 fully restores tissue invasion and parasite transmission, while replacement with the aXI domain from human integrins still partially restores liver infection. Mutations around the ligand binding site allowed salivary gland invasion but led to inefficient transmission to the rodent host. These results suggest that apicomplexan parasites appropriated polyspecific I domains in part for their ability to engage with multiple ligands and to provide traction for emigration into diverse organs in distant phyla.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Tiermedizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2050-084X
• Sprache: Englisch