{
  "id": 4355415,
  "title": "Single-Molecule Nanopore Profiling of p53-TAD Conformational Dynamics, Interactions, and Inhibition",
  "url": "https://urgent.news/2026/08/29/single-molecule-nanopore-profiling-of-p53-tad-conformational-dynamics",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-29T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747917v1?rss=1"
  },
  "original_language": "en",
  "account": "Researchers have developed a novel nanopore-based method to study the conformational dynamics and interactions of intrinsically disordered proteins (IDPs) at the single-molecule level. The technique was applied to the transactivation domain of tumor suppressor p53, a protein of significant importance in cancer biology. The study revealed that the nanopore platform, MspA, can capture p53-TAD and distinguish up to six different current states, with the protein frequently transitioning between them, showcasing a complex conformational landscape.\n\nThe nanopore was also capable of detecting the impact of a cancer-associated double mutational variant, N29K/N30D, of p53-TAD. By integrating experimental results with steered molecular dynamics simulations, the researchers found that the mutant sampled compact conformational states more often than the wild-type protein, aligning with earlier NMR studies.\n\nMoreover, the MspA platform allowed for real-time observation of the interaction between the E3 ligase MDM2 and p53-TAD, and how this binding was inhibited by the anti-cancer compound epigallocatechin gallate (EGCG). The findings showed that EGCG stabilizes one of the six conformational states sampled by p53-TAD, offering a mechanistic rationale for its inhibitory effect on the protein.\n\nIn summary, this study highlights the potential of the single-molecule nanopore platform for the label-free monitoring of IDP conformational dynamics, modulation, binding, and inhibition at an unprecedented level of detail.",
  "summary": "Investigating the conformational dynamics of intrinsically disordered proteins (IDPs) is essential to understanding how their structural heterogeneity underlies function and how their dysregulation contributes to diseases. Here, we utilized an MspA nanopore-based approach for studying the conformational dynamics and interactions of IDPs at the single-molecule level. The platform was demonstrated…",
  "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."
}