BRANCHING AND ELONGATION WITH LACTOSAMINOGLYCAN CHAINS OF N-LINKED OLIGOSACCHARIDES RESULT IN A SHIFT TOWARD TERMINATION WITH ALPHA-2-]3-LINKED RATHER THAN WITH ALPHA-2-]6-LINKED SIALIC-ACID RESIDUES

The activity of bovine colostrum CMP-NeuAc: Gal beta 1-->4GlcNAc beta-R alpha 2-->6-sialyltransferase (alpha 6-NeuAcT) toward oligosaccharides that form part of complex-type, N-linked glycans appears significantly reduced when a bisecting GlcNAc residue or additional branches are present, or when core GlcNAc residues are absent, By contrast human placenta CMP-NeuAc:Gal beta 1-->4GlcNAc beta-R alpha 2-->3-sialyltransferase (alpha 3-NeuAcT) is much less sensitive to structural variations in these accepters. Furthermore the alpha 3-NeuAcT shows a much higher activity than the alpha 6-NeuAcT with oligosaccharides that form part of linear and branched lactosaminoglycan extensions. These results indicate that, in tissues that express both enzymes, branching and lactosaminoglycan formation of N-linked glycans will cause a shift from termination with alpha 2-->6-linked sialic acid to termination with alpha 2-->3-linked sialic acid residues, These findings provide an enzymatic basis for the sialic acid linkage-type patterns found on the oligosaccharide chains of N-glycoproteins.