Taxonomic group: protista / Apicomplexa
(Phylum: Apicomplexa)
Host organism: Homo sapiens
Organ / tissue: Life stage: sporozoiteAssociated disease: malaria due to Plasmodium falciparum [ICD11:
1F40 
, ICD11:
XN69B ]
NCBI PubMed ID: 28916755Publication DOI: 10.1038/s41467-017-00571-yJournal NLM ID: 101528555Publisher: London: Nature Publishing Group
Correspondence: goddard-borger.e
wehi.edu.au; boddey
wehi.edu.au
Institutions: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia, Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia, Radboud University Medical Center, Department of Medical Microbiology, HB, 6500, Nijmegen, The Netherlands, Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, 3010, Australia, Department of Surgery, University of Alberta, Edmonton, AB, Canada, T6G 2E1
O-glycosylation of the Plasmodium sporozoite surface proteins CSP and TRAP was recently identified, but the role of this modification in the parasite life cycle and its relevance to vaccine design remain unclear. Here, we identify the Plasmodium protein O-fucosyltransferase (POFUT2) responsible for O-glycosylating CSP and TRAP. Genetic disruption of POFUT2 in Plasmodium falciparum results in ookinetes that are attenuated for colonizing the mosquito midgut, an essential step in malaria transmission. Some POFUT2-deficient parasites mature into salivary gland sporozoites although they are impaired for gliding motility, cell traversal, hepatocyte invasion, and production of exoerythrocytic forms in humanized chimeric liver mice. These defects can be attributed to destabilization and incorrect trafficking of proteins bearing thrombospondin repeats (TSRs). Therefore, POFUT2 plays a similar role in malaria parasites to that in metazoans: it ensures the trafficking of Plasmodium TSR proteins as part of a non-canonical glycosylation-dependent endoplasmic reticulum protein quality control mechanism.The role of O-glycosylation in the malaria life cycle is largely unknown. Here, the authors identify a Plasmodium protein O-fucosyltransferase and show that it is important for normal trafficking of a subset of surface proteins, particularly CSP and TRAP, and efficient infection of mosquito and vertebrate hosts.
immunology, infection, vaccine, proteins, parasites, Plasmodium falciparum
Structure type: oligomer
Location inside paper: p. 561-2, Fig. 1a, Fig. S1
Aglycon: Ser/Thr protein bearing thrombospondin repeat (TSR)
Compound class: O-glycan
Contained glycoepitopes: IEDB_136045,IEDB_142488,IEDB_142489,IEDB_144562,IEDB_146664,IEDB_152214,IEDB_174333,IEDB_983931,SB_192,SB_86
Methods: genetic methods, enzyme assay, immunoblotting, immunofluorescence microscopy, flow cytometry analysis, hepatocyte invasion assay
Enzymes that release or process the structure: protein O-fucosyltransferase (POFUT2), β-1,3-glucosyltransferase (B3GLCT)
NCBI Taxonomy refs (TaxIDs): 5833
Show glycosyltransferases
There is only one chemically distinct structure:
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