{
  "id": 9625967,
  "title": "Brain Landscape In Situ Crosslinking Mass Spectrometry (BLIS-XL-MS) Enables Global Analysis of Protein Structural Remodeling in the Brain",
  "url": "https://urgent.news/2026/09/24/brain-landscape-in-situ-crosslinking-mass-spectrometry-blis-xl-ms",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-24T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.16.752161v1?rss=1"
  },
  "original_language": "en",
  "account": "Pathological protein conformational changes are a crucial characteristic of brain disorders. Traditional methods for understanding protein conformational alterations are targeted and challenging to scale for comprehensive proteome-wide examination. Recent mass spectrometry-based structural proteomic techniques have expanded coverage, yet they frequently entail intricate workflows and trade-offs between labeling efficiency and maintaining the in vivo molecular state. Consequently, quantitative analysis of proteome-wide structural remodeling has remained constrained.\n\nWe introduce Brain Landscape In Situ Crosslinking Mass Spectrometry (BLIS-XL-MS), a novel experimental and computational framework aimed at analyzing protein and protein-complex remodeling within brain tissues. BLIS-XL-MS ensures the molecular state remains stable before secondary crosslinking, enhances reagent accessibility through sectioning and permeabilization, and seamlessly integrates quantitative crosslink analysis with structural and protein-interaction-network interpretation. When applied to brains from GluA1A636T knock-in mice, which model a neurodevelopmental disorder, BLIS-XL-MS unveiled a coordinated remodeling of protein systems involved in AMPA receptor-trafficking, mitochondrial function, and cell-death pathways. We demonstrate that BLIS-XL-MS offers a scalable framework for mapping disease-associated structural remodeling throughout the entire brain proteome.",
  "summary": "Pathological protein conformational remodeling is a key molecular feature of brain disorders. However, conventional approaches to understand the changes in potein conformation are targeted and difficult to scale proteome-wide analysis. Emerging mass spectrometry-based structural proteomic methods broaden coverage but often involve complex workflows and trade-offs between labeling efficiency and…",
  "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."
}