{
  "id": 18130999,
  "title": "The mechanism of cysteine sensing by LRRC58",
  "url": "https://urgent.news/2026/11/04/the-mechanism-of-cysteine-sensing-by-lrrc58",
  "topic": "science",
  "section": "Science",
  "published": "2026-11-04T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763985v1?rss=1"
  },
  "original_language": "en",
  "account": "Cysteine, a vital amino acid for life, can become toxic when present in excessive amounts. Cells and tissues are constantly exposed to elevated levels of cysteine from both internal and external sources, yet they manage to maintain low intracellular concentrations to ensure proper functioning and prevent premature death. Researchers have now uncovered a mechanism by which cells sense cysteine levels and regulate their abundance to keep toxicity at bay. Utilizing cryo-electron microscopy, scientists have determined the structures of the CRL5LRRC58 E3 ligase, both alone and in complex with the cysteine-catabolizing enzyme CDO1. Their findings reveal that CDO1 interacts with LRRC58 near a zinc-coordinating cysteine motif. Upon exposure to cysteine, Cys296 within this motif undergoes covalent modification. This modification, coupled with the ejection of zinc from the motif, triggers significant structural rearrangements in LRRC58, which are propagated through Cys319. The reorientation resulting from these changes destabilizes CDO1 binding and positions LRRC58's Lys111 for autoubiquitylation. This repositioning of LRRC58 allows CDO1 to accumulate, effectively lowering intracellular cysteine levels. However, mutating Cys319 disrupts the inhibitory rearrangement of LRRC58 upon cysteine modification, rendering the ligase constitutively active and hindering CDO1 stabilization. Consequently, this leads to systemic cysteine accumulation and premature death in animal models. These insights provide a molecular basis for the homeostatic cysteine sensing mechanism by LRRC58, highlighting its crucial role in maintaining cysteine concentrations compatible with a healthy life.",
  "summary": "Cysteine is essential for life but toxic in excess. Cells and tissues are exposed to elevated cysteine from endogenous sources and the environment yet maintain low intracellular concentrations to sustain life. Here we identify a mechanism for sensing cysteine to control its abundance and prevent toxicity and premature death. Using cryo-electron microscopy we determine structures of the…",
  "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."
}