Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan.

Molecular & Cellular Proteomics : MCP
Miyako NakanoYasuhiko Kizuka

Abstract

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.

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Citations

Jul 29, 2020·Frontiers in Chemistry·Qiushi ChenYan Ren
Jan 16, 2020·International Journal of Molecular Sciences·Masamichi NagaeYasuhiko Kizuka
Mar 21, 2020·International Journal of Molecular Sciences·Zhipeng SuYunsen Li
Aug 23, 2020·International Journal of Molecular Sciences·Chenyu MaYasuhiko Kizuka
Dec 31, 2019·Biochimica Et Biophysica Acta. General Subjects·Misuzu HashimotoYasuhiko Kizuka
Oct 23, 2020·Nature Reviews. Molecular Cell Biology·Katrine T SchjoldagerHenrik Clausen

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