Biosynthesis of glycosyl-phosphatidylinositol lipids in Trypanosoma brucei: involvement of mannosyl-phosphoryldolichol as the mannose donor.
Trypanosome variant surface glycoproteins (VSGs) exemplify a class of eukaryotic cell-surface glycoproteins that rely on a covalently attached lipid, glycosyl-phosphatidylinositol, for membrane attachment. The glycolipid anchor is acquired soon after translation of the polypeptide, apparently by replacement of a short sequence of carboxyl-terminal amino acids with a precursor glycolipid. A candidate glycolipid precursor (P2) and a related glycolipid (P3) have been identified in polar lipid extracts from trypanosomes. Both lipids are glycosylphosphatidylinositol species containing a Man3GlcN core glycan indistinguishable from the backbone sequence of the VSG glycolipid anchor. We and others have recently described the cell-free synthesis of P2, P3, and a spectrum of putative biosynthetic lipid intermediates using crude preparations of trypanosome membranes. In this paper we use these preparations to show that all three mannose residues in the glycosyl-phosphatidylinositol glycan are derived from dolichol-P-mannose.
Menon
A K
AK
Laboratory of Molecular Parasitology, Rockefeller University, New York, NY 10021.
Mayor
S
S
Schwarz
R T
RT
D000818:Animals; D001665:Binding Sites; D002240:Carbohydrate Sequence; D002474:Cell-Free System; D004287:Dolichol Monophosphate Mannose / Q000494:pharmacology*; D006017:Glycolipids / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols; D008358:Mannose / Q000378:metabolism*; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism*; D014316:Tritium; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000378:metabolism*
D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D010716:Phosphatidylinositols; D014316:Tritium; D004287:Dolichol Monophosphate Mannose; D008358:Mannose