AI Article Synopsis
- Glycoproteins rely on complex glycans for their functions, but how complex glycan biosynthesis is regulated remains unclear.
- Researchers discovered that bisecting GlcNAc suppresses the formation of certain terminal sugar structures on glycans, affecting immune system response.
- The study revealed that enzymes prefer nonbisected glycans, leading to increased expression of these terminal structures in mice lacking the bisecting GlcNAc biosynthetic enzyme, GnT-III.
Article 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 -glycan, suppresses the biosynthesis of various types of terminal epitopes in -glycans, including fucose, sialic acid and human natural killer-1. Expression of these epitopes in -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 -glycan terminals were revealed to prefer a nonbisected -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 -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 -glycosylation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773561 | PMC |
| http://dx.doi.org/10.1074/mcp.RA119.001534 | DOI Listing |
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