{
  "id": 6178249,
  "title": "Molecular Determinants of Sequence-Dependent N-glycosylation by the Human Oligosaccharyltransferase",
  "url": "https://urgent.news/2026/09/07/molecular-determinants-of-sequence-dependent-n-glycosylation-by-the",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-07T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.03.749169v1?rss=1"
  },
  "original_language": "en",
  "account": "The molecular determinants of sequence-dependent N-glycosylation by the human oligosaccharyltransferase (OST) complex are being investigated through a combination of advanced computational methods and experimental analyses. Researchers have constructed the first atomistic model of human OST, incorporating both the lipid-linked oligosaccharide donor and an acceptor peptide within a catalytically competent complex. Simulations reveal that conserved STT3 motifs stabilize the acceptor Asn, explaining how substitutions at positions 0, +1, and +2 impact binding and productive geometry. Cellular assays in HEK 293T cells confirm the predicted loss of glycosylation for specific sequons, including N0Q, +1 Pro, and the +2 hierarchy Thr-Ser-Cys pattern. The analysis of 14,800 human glycosites supports these rules at a proteome scale, shedding light on the molecular basis of sequence-dependent N-glycosylation by the human OST complex.",
  "summary": "Protein N-glycosylation is catalysed by the oligosaccharyltransferase (OST) complex, yet how local sequon composition controls substrate selection by human OST remains poorly understood. Here we combine atomistic molecular dynamics, alchemical free-energy calculations, in cellulo glycosylation assays and human glycoproteome analysis to define the molecular basis of sequence-dependent…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}