The diversity of dolichol-linked precursors to Asn-linked glycans likely results from secondary loss of sets of glycosyltransferases

Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1548-53. doi: 10.1073/pnas.0409460102. Epub 2005 Jan 21.

Abstract

The vast majority of eukaryotes (fungi, plants, animals, slime mold, and euglena) synthesize Asn-linked glycans (Alg) by means of a lipid-linked precursor dolichol-PP-GlcNAc2Man9Glc3. Knowledge of this pathway is important because defects in the glycosyltransferases (Alg1-Alg12 and others not yet identified), which make dolichol-PP-glycans, lead to numerous congenital disorders of glycosylation. Here we used bioinformatic and experimental methods to characterize Alg glycosyltransferases and dolichol-PP-glycans of diverse protists, including many human pathogens, with the following major conclusions. First, it is demonstrated that common ancestry is a useful method of predicting the Alg glycosyltransferase inventory of each eukaryote. Second, in the vast majority of cases, this inventory accurately predicts the dolichol-PP-glycans observed. Third, Alg glycosyltransferases are missing in sets from each organism (e.g., all of the glycosyltransferases that add glucose and mannose are absent from Giardia and Plasmodium). Fourth, dolichol-PP-GlcNAc2Man5 (present in Entamoeba and Trichomonas) and dolichol-PP- and N-linked GlcNAc2 (present in Giardia) have not been identified previously in wild-type organisms. Finally, the present diversity of protist and fungal dolichol-PP-linked glycans appears to result from secondary loss of glycosyltransferases from a common ancestor that contained the complete set of Alg glycosyltransferases.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Asparagine*
  • Bacteria / enzymology
  • Bacteria / genetics
  • Computational Biology
  • Dolichols / metabolism*
  • Evolution, Molecular
  • Genetic Variation*
  • Glycopeptides / biosynthesis
  • Glycosyltransferases / genetics
  • Glycosyltransferases / metabolism*
  • Humans
  • Polysaccharides / chemistry*
  • Species Specificity

Substances

  • Dolichols
  • Glycopeptides
  • Polysaccharides
  • Asparagine
  • Glycosyltransferases