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

Glycobiology. 2018 May 1;28(5):333-343. doi: 10.1093/glycob/cwy013.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Caenorhabditis elegans / enzymology
  • Cricetulus
  • Mannosyltransferases / metabolism*
  • Plasmodium falciparum / enzymology
  • Plasmodium falciparum / metabolism*
  • Protozoan Proteins / metabolism*
  • Thrombospondin 1 / metabolism*
  • Toxoplasma / enzymology
  • Toxoplasma / metabolism*

Substances

  • Protozoan Proteins
  • Thrombospondin 1
  • thrombospondin-related adhesive protein, protozoan
  • Mannosyltransferases