Substrate Preference and Interplay of Fucosyltransferase 8 and N‑Acetylglucosaminyltransferases

• Published in: Journal of the American Chemical Society Vol. 139; no. 28; pp. 9431 - 9434
• Main Authors: Tseng, Tzu-Hao, Lin, Tzu-Wen, Chen, Chien-Yu, Chen, Chein-Hung, Lin, Jung-Lee, Hsu, Tsui-Ling, Wong, Chi-Huey
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.07.2017
• Subjects: disease course; glycopeptides; glycoproteins; glycosylation; glycosyltransferases; humans; N-acetylglucosamine; neoplasms; polysaccharides; postnatal development; substrate specificity
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.7b03729

The core fucosylation of N-glycans on glyco­proteins is catalyzed by fucosyl­transferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and post­natal development. The substrate specificity of FUT8 toward bi-antennary N-glycans has been reported, but it is unclear with regard to tri-antennary and tetra-antennary glycans. Here, we examined the specificity and activity of human FUT8 toward tri- and tetra-antennary N-glycans in the forms of glyco­peptides. We found that the tri-antennary glycan [A3­(2,4,2) type] terminated with N-acetyl­glucos­amine (GlcNAc), which is generated by N-acetyl­glucos­aminyl­transferase (GnT)-IV, is a good substrate for FUT8, but the A3­(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. We also observed that core fucosyl­ation reduced the activity of GnT-IV toward the bi-antennary glycan. Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyl­transferases, particularly GnT-IV, play important roles in directing the branching and core fucosyl­ation of N-glycans in vivo. This study thus provides insights into the interplay among FUT8, GnT-IV, and GnT-V in N-linked glycosyl­ation during the assembly of glycoproteins.