Journal
MOLECULAR & CELLULAR PROTEOMICS
Volume 18, Issue 10, Pages 2044-2057Publisher
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DOI: 10.1074/mcp.RA119.001534
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Funding
- Japan Society for the Promotion of Science (JSPS) [17K07356]
- Takeda Science Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Grants-in-Aid for Scientific Research [17K07356] Funding Source: KAKEN
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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 Nglycosylation.
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