{
  "id": 3491434,
  "title": "Cryo-EM structures of apo human Factor XIa reveal catalytic-domain flexibility and exposure of the Factor IX-binding site",
  "url": "https://urgent.news/2026/08/26/cryo-em-structures-of-apo-human-factor-xia-reveal-catalytic-domain",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-26T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.25.744604v1?rss=1"
  },
  "original_language": "en",
  "account": "Factor XI (FXI), a vital coagulation protease in the intrinsic blood coagulation pathway, holds promise as an antithrombotic target. However, the transformation of FXI from its inactive zymogen state to the active FXIa has remained elusive. A recent study employing cryo-electron microscopy (cryo-EM) has shed light on this transformation process.\n\nThe research reveals that the activation of FXI triggers a comprehensive restructuring of the homodimer, extending beyond the activation loop to encompass a considerable reorientation of the catalytic domain (CD) in relation to the apple-domain (AD) platform. This CD exhibits significant conformational variability, with the researchers identifying three distinct conformers. These findings suggest that FXIa exists as a dynamic ensemble rather than a rigid structure.\n\nThe activation process disrupts the allosteric communication between the catalytic domains present in the zymogen, thereby facilitating this structural flexibility. This increased plasticity in the CD allows for the dynamic exposure of the A3 exosite, a critical site for the binding of Factor IX. Interestingly, a comparison with plasma kallikrein (PKa), another apple-domain-containing contact-system protease, indicates that such structural flexibility may be a shared characteristic among these types of proteases.\n\nThese findings provide a structural framework for understanding substrate recognition by FXIa and identify novel, non-catalytic sites for the development of specific inhibitors against FXIa.",
  "summary": "Factor XI (FXI) is a key coagulation protease of the intrinsic pathway of blood coagulation and an emerging antithrombotic target. However, the structural transition from zymogen to active Factor XIa (FXIa) has remained poorly understood. Using cryo-EM, we demonstrate that FXI activation results in a global reorganization of the homodimer, extending beyond the activation loop to include a…",
  "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."
}