Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Quantitative glycoproteomics provides insight into regulated enzyme activity during N-glycosylation stress conditions (#509)

Danila Elango 1 , Ben L. Schulz 1
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia

Asparagine (N)- linked glycosylation is a common and important post-translational modification (PTM) present in all three domains of life - archaea, eukaryota and bacteria. It has several essential roles including facilitating protein folding, stability and function. It specifically refers to the attachment of carbohydrates onto asparagine (Asn) residues, typically within the consensus sequon N-X-S/T, where X cannot be proline. Biosynthesis of the donor glycan substrate for glycosylation is a multi-enzymatic process catalysed by the Alg (asparagine-linked glycosyltransferase) enzymes (Alg1-14). The sequential activity of the Alg enzymes results in a 14-sugar oligosaccharide (Glc3Man9GlcNAc2) that is transferred onto a protein acceptor substrate by the oligosaccharyltransferase (OTase). Defects in the N-glycan biosynthetic pathway cause changes in glycan occupancy, structure, and changes in protein abundance. While the oligosaccharyltransferase (OTase) is the central enzyme in N-glycoprotein biosynthesis, physiological regulation of the enzyme is poorly understood. To test for the presence of a regulatory mechanism controlling OTase activity in response to glycosylation stress, we used SWATH-MS to quantify site-specific changes in glycan occupancy in a yeast model system. We compared site-specific glycosylation in yeast with defects in LLO structure (alg6Δ) and abundance (tunicamycin-treated cells). We identified a subset of sites that were inefficiently glycosylated in tunicamycin-treated cells but which remained efficiently glycosylated in alg6∆ cells. Our observations were consistent when we used the tetracycline-repressible system to knockdown ALG6 and ALG7. Our findings suggest that sequence motifs regulate site-specific OTase activity to ensure glycosylation is optimally targeted in conditions of glycosylation stress.