{
  "id": 2741642,
  "title": "Autotransporter folding avoids a kinetic trap during vectorial translocation across the bacterial outer membrane",
  "url": "https://urgent.news/2026/08/22/autotransporter-folding-avoids-a-kinetic-trap-during-vectorial",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-22T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.22.746429v1?rss=1"
  },
  "original_language": "en",
  "account": "Autotransporter proteins play a significant role as virulence factors in Gram-negative pathogens. However, the exact mechanism of their folding during secretion is still unclear. One puzzling aspect is the contrast between the rapid folding and secretion of pertactin in vivo within minutes and its much slower refolding in vitro, which can take hours to days. To address this issue, researchers developed the BEAM framework, a multiscale approach that utilizes coarse-grained simulations and machine learning to identify slow collective variables and guide all-atom enhanced sampling.\n\nWhen applied to a specific segment of the pertactin passenger domain from Bordetella pertussis, BEAM demonstrated significantly greater conformational coverage compared to conventional methods. This analysis revealed a compact, non-native intermediate state that is accessible in solution but incompatible with the process of vectorial translocation across the bacterial outer membrane. The researchers found that the presence of this intermediate state slows down the folding process. Conversely, removing this intermediate allows for faster, folding kinetics akin to those observed in vivo.\n\nThe combined insights from these findings provide a comprehensive explanation for how the vectorial secretion pathway effectively accelerates pertactin folding by avoiding this off-pathway kinetic trap. Beyond its immediate implications for understanding pertactin's behavior, the BEAM framework offers a versatile strategy for uncovering hidden conformational states at atomic resolution across various biological systems.",
  "summary": "Autotransporter proteins are major virulence factors in Gram-negative pathogens, yet how they fold during secretion remains incompletely understood. A longstanding puzzle is why pertactin folds and is secreted in vivo within minutes but refolds in vitro over hours to days. We introduce BEAM, a multiscale framework that learns slow collective variables from coarse-grained simulations to guide…",
  "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."
}