Apicomplexan C-mannosyltransferases modify thrombospondin type I-containing adhesins of the TRAP family

Hoppe, C. M., Albuquerque-Wendt, A. , Bandini, G., Leon, D. R., Scherbakova, A., Buettner, F. F.R., Izquierdo, L., Costello, C. E., Bakker, H. and Routier, F. H. (2018) Apicomplexan C-mannosyltransferases modify thrombospondin type I-containing adhesins of the TRAP family. Glycobiology, 28(5), pp. 333-343. (doi: 10.1093/glycob/cwy013) (PMID:29432542) (PMCID:PMC6018953)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Albuquerque-Wendt, Ms Andreia
• Authors: Hoppe, C. M., Albuquerque-Wendt, A., Bandini, G., Leon, D. R., Scherbakova, A., Buettner, F. F.R., Izquierdo, L., Costello, C. E., Bakker, H., and Routier, F. H.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Glycobiology
• Publisher: Oxford University Press
• ISSN: 0959-6658
• ISSN (Online): 1460-2423
• Published Online: 08 February 2018