The nature and extent of carbohydrate modification in intraerythrocytic stage Plasmodium falciparum proteins have been controversial. This study describes the characterization of the carbohydrates in intraerythrocytic P. falciparum proteins and provides an overall picture of the nature of carbohydrate modification in the parasite proteins. P. falciparum strains were metabolically labeled with radioactive sugar precursors and ethanolamine at different developmental stages. The individual parasite proteins separated on SDS-polyacrylamide gels and whole parasite cell lysates were analyzed for the carbohydrate moieties. The results established the following: 1) glycosylphosphatidylinositol (GPI) anchors represent the major carbohydrate modification in the intraerythrocytic stage P. falciparum proteins; 2) in contrast to previous reports, O-linked carbohydrates are either absent or present only at very low levels in the parasite; and 3) P. falciparum contains low levels of N-glycosylation capability. The amount of N-linked carbohydrates in whole parasite proteins is ϳ6% compared with the GPI anchors attached to proteins based on radioactive GlcN incorporated into the proteins.The glycan cores of multiple parasite protein GPI anchors are all similar, consisting of protein-ethanolamine-phosphate-(Man␣1-2)6Man␣1-2Man␣1-6Man␣1-4GlcN. The fourth Man residues distal to GlcN of the GPI anchor glycan cores contain unidentified substituents that are susceptible to conditions of nitrous acid deamination. This unusual structural feature may contribute to the reported pathogenic properties of the P. falciparum GPI anchors.Malaria, a life-threatening disease caused by parasitic protozoa of the genus Plasmodium, is a major health problem throughout the tropical and subtropical regions of the world. Among the four species that infect humans, Plasmodium falciparum is the most virulent. New approaches such as vaccine development and novel therapeutic agents are urgently needed due to the emergence of parasite strains resistant to chloroquine and other commonly used drugs (1).Vaccines based on antigens of the blood stage parasite are under intensive study. A major focus has been on synthetic peptides or recombinant proteins of cell surface antigens (2-6). However, this approach has not been highly effective, although immunization with native cell surface proteins purified from the erythrocytic stage parasite is known to confer significant protective immunity (7-10). It is plausible that post-translational modifications play an important role in antigenicity. Accordingly, a basic understanding of such modifications may assist in the development of effective vaccines.Glycosylation is an often extensive post-translational modification of eukaryotic proteins. Carbohydrate moieties of glycoproteins perform a variety of functions including modulation of immunological properties, receptor-ligand interactions, sorting and localization of proteins, cell adhesion, and cell-cell communication (11). In addition, they contribute to protein conform...
Carbohydrates fulfil many common as well as extremely important functions in nature. They show a variety of molecular displays--e.g., free mono-, oligo-, and polysaccharides, glycolipids, proteoglycans, glycoproteins, etc.--with particular roles and localizations in living organisms. Structure-specific peculiarities are so many and diverse that it becomes virtually impossible to cover them all from an analytical perspective. Hence this manuscript, focused on mammalian glycosylation, rather than a complete list of analytical descriptors or recognized functions for carbohydrate structures, comprehensively reviews three central issues in current glycoscience, namely (i) structural analysis of glycoprotein glycans, covering both classical and novel approaches for teasing out the structural puzzle as well as potential pitfalls of these processes; (ii) an overview of functions attributed to carbohydrates, covering from monosaccharide to complex, well-defined epitopes and full glycans, including post-glycosylational modifications, and (iii) recent technical advances allowing structural identification of glycoprotein glycans with simultaneous assignation of biological functions.
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