Apicomplexan C-Mannosyltransferases Modify Thrombospondin Type I-containing Adhesins of the TRAP Family.

In many metazoan species， an unusual type of protein glycosylation， called C-mannosylation， occurs on adhesive thrombospondin type 1 repeats (TSRs) and type I cytokine receptors. This modification has been shown to be catalyzed by the Caenorhabditis elegans DPY-19 protein and orthologues of the encoding gene were found in the genome of apicomplexan parasites. Lately， the micronemal adhesin thrombospondin-related anonymous protein (TRAP) was shown to be C-hexosylated in Plasmodium falciparum sporozoites. Here， we demonstrate that also the micronemal protein MIC2 secreted by Toxoplasma gondii tachyzoites is C-hexosylated. When expressed in a mammalian cell line deficient in C-mannosylation， P. falciparum and T. gondii Dpy19 homologs were able to modify TSR domains of the micronemal adhesins TRAP/MIC2 family involved in parasite motility and invasion. In vitro， the apicomplexan enzymes can transfer mannose to a WXXWXXC peptide but， in contrast to C. elegans or mammalian C-mannosyltransferases， are inactive on a short WXXW peptide. Since TSR domains are commonly found in apicomplexan surface proteins， C-mannosylation may be a common modification in this phylum.