Bisecting GlcNAc is a general suppressor of terminal modification of N-glycan

Miyako Nakano, Sushil K. Mishra, Yuko Tokoro, Keiko Sato, Kazuki Nakajima, Yoshiki Yamaguchi, Naoyuki Taniguchi, Yasuhiko Kizuka

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


Glycoproteins are decorated with complex glycans for protein functions. However, regulation mechanisms of complex glycan biosynthesis are largely unclear. Here we found that bisecting GlcNAc, a branching sugar residue in N-glycan, suppresses the biosynthesis of various types of terminal epitopes in N-glycans, including fucose, sialic acid and human natural killer-1. Expression of these epitopes in N-glycan was elevated in mice lacking the biosynthetic enzyme of bisecting GlcNAc, GnT-III, and was conversely suppressed by GnT-III overexpression in cells. Many glycosyltransferases for N-glycan terminals were revealed to prefer a nonbisected N-glycan as a substrate to its bisected counterpart, whereas no up-regulation of their mRNAs was found. This indicates that the elevated expression of the terminal N-glycan epitopes in GnT-III-deficient mice is attributed to the substrate specificity of the biosynthetic enzymes. Molecular dynamics simulations further confirmed that nonbisected glycans were preferentially accepted by those glycosyltransferases. These findings unveil a new regulation mechanism of protein N-glycosylation.

Original languageEnglish
Pages (from-to)2044-2057
Number of pages14
JournalMolecular and Cellular Proteomics
Issue number10
Publication statusPublished - 2019

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology


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