Glycosyl-sn-1,2-dimyristylphosphatidylinositol is covalently linked to Trypanosoma brucei variant surface glycoprotein.
The COOH terminus of the externally disposed variant surface glycoprotein (VSG) of the eukaryotic pathogenic protozoan Trypanosoma brucei strain 427 variant MITat 1.4 (117) is covalently linked to a novel phosphatidylinositol-containing glycolipid. This conclusion is supported by analysis of the products of nitrous acid deamination or Staphylococcus aureus phosphatidylinositol-specific phospholipase C treatment of purified membrane-form VSG. Lysis of trypanosomes is accompanied by release of soluble VSG, catalyzed by activation of an endogenous phospholipase C. The only apparent difference between membrane-form VSG and soluble VSG is the removal of sn-1,2-dimyristylglycerol. The COOH-terminal glycopeptide derived by Pronase digestion of soluble VSG was characterized by chemical modification and digestion with alkaline phosphatase. The results are consistent with the single non-N-acetylated glucosamine residue being the reducing terminus of the oligosaccharide and in a glycosidic linkage to a myo-inositol monophosphate that is probably myo-inositol 1,2-cyclic monophosphate. A partial structure for the VSG COOH-terminal moiety is presented. This structure represents a new type of eukaryotic post-translational protein modification and membrane anchor. We discuss the relevance of this structure to observations that have been made with other eukaryotic membrane proteins.
D000818:Animals; D002241:Carbohydrates / Q000032:analysis; D002849:Chromatography, Gas; D008401:Gas Chromatography-Mass Spectrometry; D006017:Glycolipids / Q000378:metabolism*; D006020:Glycopeptides / Q000032:analysis; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis; D010715:Phosphatidylglycerols; D010716:Phosphatidylinositols / Q000378:metabolism*; D011402:Pronase; D011485:Protein Binding; D014316:Tritium; D014346:Trypanosoma brucei brucei / Q000378:metabolism*; D014643:Variant Surface Glycoproteins, Trypanosoma
D002241:Carbohydrates; D006017:Glycolipids; D006020:Glycopeptides; D006023:Glycoproteins; D009227:Myristic Acids; D010446:Peptide Fragments; D010715:Phosphatidylglycerols; D010716:Phosphatidylinositols; D014643:Variant Surface Glycoproteins, Trypanosoma; D019814:Myristic Acid; D014316:Tritium; C002773:dimyristoylphosphatidylglycerol; D011402:Pronase