{
  "id": 10531914,
  "title": "Deep-learning-based design of an orthogonal self-labeling protein from K-Ras(G12C)",
  "url": "https://urgent.news/2026/09/28/deep-learning-based-design-of-an-orthogonal-self-labeling-protein",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-28T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.27.754867v1?rss=1"
  },
  "original_language": "en",
  "account": "Self-labeling protein tags are invaluable tools for tracking proteins in living cells, yet only a handful exist, restricting the ability to observe multiple proteins simultaneously. Researchers have now devised an innovative, third, mutually exclusive SLP system using the oncoprotein K-Ras(G12C) and its covalent inhibitors. Utilizing a deep-learning-based methodology, they meticulously redesigned the K-Ras(G12C) sequence while maintaining its covalent-inhibitor binding site. The resulting LUCI-tag is a compact 19 kDa protein capable of forming stable bonds with a wide range of K-Ras(G12C) inhibitors, each carrying diverse chemical payloads. The novel tag's speed and versatility in covalently reacting with inhibitors surpass those of existing SLPs, HaloTag7 and SNAP-tag, particularly when dealing with negatively charged payloads. Structural analysis via X-ray crystallography confirmed the tag's accuracy and revealed a preorganized inhibitor-binding pocket responsible for its rapid labeling kinetics. Extensive testing demonstrated that LUCI-tag remains biologically inactive, making it a safe and effective labeling tool. Demonstrating the practicality of their approach, LUCI-tag facilitated rapid, non-invasive live-cell imaging and enabled simultaneous three-color multiplexed experiments alongside HaloTag7 and SNAP-tag. This groundbreaking work establishes LUCI-tag as a valuable orthogonal SLP, showcasing the potential for repurposing covalent drug-target pairs into a versatile platform for protein labeling.",
  "summary": "Self-labeling protein (SLP) tags enable versatile labeling of proteins in live cells, yet only two SLPs are commonly used, limiting multiplexing. Here, we repurposed the oncoprotein K-Ras(G12C) and its covalent inhibitors to create a third, orthogonal SLP system. We used a deep-learning-based approach to radically redesign the sequence of K-Ras(G12C) while preserving its covalent-inhibitor…",
  "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."
}