Two Paralogous Gb3/CD77 Synthases in Birds Show Different Preferences for Their Glycoprotein and Glycosphingolipid Substrates

Int J Mol Sci. 2021 Sep 9;22(18):9761. doi: 10.3390/ijms22189761.

Abstract

Most glycosyltransferases show remarkable gross and fine substrate specificity, which is reflected in the old one enzyme-one linkage paradigm. While human Gb3/CD77 synthase is a glycosyltransferase that synthesizes the Galα1→4Gal moiety mainly on glycosphingolipids, its pigeon homolog prefers glycoproteins as acceptors. In this study, we characterized two Gb3/CD77 synthase paralogs found in pigeons (Columba livia). We evaluated their specificities in transfected human teratocarcinoma 2102Ep cells by flow cytofluorometry, Western blotting, high-performance thin-layer chromatography, mass spectrometry and metabolic labelling with 14C-galactose. We found that the previously described pigeon Gb3/CD77 synthase (called P) can use predominately glycoproteins as acceptors, while its paralog (called M), which we serendipitously discovered while conducting this study, efficiently synthesizes Galα1→4Gal caps on both glycoproteins and glycosphingolipids. These two paralogs may underlie the difference in expression profiles of Galα1→4Gal-terminated glycoconjugates between neoavians and mammals.

Keywords: Gb3/CD77 synthase; Shiga toxin; birds; glycosyltransferase.

MeSH terms

  • Animals
  • Birds / metabolism*
  • Galactosyltransferases / genetics
  • Galactosyltransferases / metabolism*
  • Gene Expression
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Glycosphingolipids / metabolism*
  • Glycosylation
  • Humans
  • Substrate Specificity

Substances

  • Glycoproteins
  • Glycosphingolipids
  • Galactosyltransferases
  • UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase