The lectin domain of UDP-N-acetyl-D-galactosamine: Polypeptide N-acetylgalactosaminyltransferase-T4 directs its glycopeptide specificities

Helle Hassan, Celso A. Reis, Eric Paul Bennett, Ekaterina Mirgorodskaya, Peter Roepstorff, Michael A. Hollingsworth, Joy Burchell, Joyce Taylor-Papadimitriou, Henrik Clausen

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123 Scopus citations

Abstract

The initiation step of mucin-type O-glycosylation is controlled by a large family of homologous UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-transferases). Differences in kinetic properties, substrate specificities, and expression patterns of these isoenzymes provide for differential regulation of O-glycan attachment sites and density. Recently, it has emerged that some GalNAc-transferase isoforms in vitro selectively function with partially GalNAc O-glycosylated acceptor peptides rather than with the corresponding unglycosylated peptides. O-Glycan attachment to selected sites, most notably two sites in the MUC1 tandem repeat, is entirely dependent on the glycosylation-dependent function of GalNAc-T4. Here we present data that a putative lectin domain found in the C terminus of GalNAc-T4 functions as a GalNAc lectin and confers its glycopeptide specificity. A single amino acid substitution in the lectin domain of a secreted form of GalNAc-T4 selectively blocked GalNAc-glycopeptide activity, while the general activity to peptides exerted by this enzyme was unaffected. Furthermore, the GalNAc-glycopeptide activity of wild-type secreted GalNAc-T4 was selectively inhibited by free GalNAc, while the activity with peptides was unaffected.

Original languageEnglish (US)
Pages (from-to)38197-38205
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number49
DOIs
StatePublished - Dec 8 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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