Taxonomic group: protista / Apicomplexa
(Phylum: Apicomplexa)
Associated disease: malaria due to Plasmodium falciparum [ICD11:
1F40 
, ICD11:
XN69B ]
NCBI PubMed ID: 39002668Publication DOI: 10.1016/j.jbc.2024.107557Journal NLM ID: 2985121RPublisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Correspondence: Ferguson MAJ <m.a.j.ferguson
dundee.ac.uk>; Sinnis P <psinnis1
jhu.edu>
Institutions: Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, UK, Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA, Johns Hopkins Malaria Institute, Johns Hopkins University, Baltimore, Maryland, USA, Department of Medical Parsitology, New York University School of Medicine, New York, New York, USA, Institute for Systems Biology, Seattle, Washington, USA
Glycosylphosphatidylinositol (GPI) anchor protein modification in Plasmodium species is well known and represents the principal form of glycosylation in these organisms. The structure and biosynthesis of GPI anchors of Plasmodium spp. has been primarily studied in the asexual blood stage of Plasmodium falciparum and is known to contain the typical conserved GPI structure of EtN-P-Man3GlcN-PI. Here, we have investigated the circumsporozoite protein (CSP) for the presence of a GPI anchor. CSP is the major surface protein of Plasmodium sporozoites, the infective stage of the malaria parasite. While it is widely assumed that CSP is a GPI-anchored cell surface protein, compelling biochemical evidence for this supposition is absent. Here, we employed metabolic labeling and mass-spectrometry-based approaches to confirm the presence of a GPI anchor in CSP. Biosynthetic radiolabeling of CSP with [3H]-palmitic acid and [3H]-ethanolamine, with the former being base-labile and therefore ester-linked, provided strong evidence for the presence of a GPI anchor on CSP, but these data alone were not definitive. To provide further evidence, immunoprecipitated CSP was analyzed for the presence of myo-inositol (a characteristic component of GPI anchor) using strong acid hydrolysis and GC-MS for highly sensitive and quantitative detection. The single ion monitoring (SIM) method for GC-MS analysis confirmed the presence of the myo-inositol component in CSP. Taken together, these data provide confidence that the long-assumed presence of a GPI anchor on this important parasite protein is correct
Glycosylphosphatidylinositol, GC-MS, Plasmodium, Malaria, circumsporozoite protein (CSP), metabolic labeling, sporozoite
Structure type: oligomer
Location inside paper: pg. 3, Fig. 2, A
Compound class: GPI-anchor
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_130701,IEDB_136104,IEDB_140116,IEDB_141793,IEDB_141807,IEDB_141829,IEDB_141830,IEDB_141832,IEDB_143632,IEDB_144983,IEDB_151531,IEDB_152206,IEDB_153220,IEDB_474450,IEDB_76933,IEDB_983930,SB_136,SB_191,SB_196,SB_198,SB_44,SB_67,SB_72
Related record ID(s): 4846, 5448, 5449
NCBI Taxonomy refs (TaxIDs): 5833
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
report error