{
  "id": 7248996,
  "title": "Human NHE1 binds full-length calcineurin with high affinity and inhibits substrate dephosphorylation",
  "url": "https://urgent.news/2026/09/13/human-nhe1-binds-full-length-calcineurin-with-high-affinity-and",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-13T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750614v1?rss=1"
  },
  "original_language": "en",
  "account": "Calcineurin (Cn) engages with the Na+/H+-exchanger NHE1 via its calcineurin-binding domain (NHE1-CnBD). The manner in which full-length human Cn affects this interaction and its implications has been unclear until now. Researchers utilized fluorescence anisotropy and quantitative size-exclusion chromatography to measure the interaction between full-length human Cn and NHE1-CnBD in various activation states. Activation of Cn via Ca2+/calmodulin increased the affinity for NHE1-CnBD from a submicromolar range to tens of nanomolar, and stabilized the complex. Notably, NHE1-CnBD displaced the immunosuppressive cyclosporin A/cyclophilin A complex from binding to Cn, and selectively inhibited the dephosphorylation of a phosphopeptide substrate. However, it enhanced the hydrolysis of p-nitrophenyl phosphate. These results establish NHE1 as a high-affinity, substrate-competitive regulator of calcineurin, inhibiting substrate recognition rather than catalysis. This discovery offers a mechanistic framework for the reciprocal regulation between Cn and NHE1.",
  "summary": "Calcineurin (Cn) interacts with the Na+/H+-exchanger NHE1 through its calcineurin-binding domain (NHE1-CnBD). How activation of full-length Cn influences this interaction and its functional consequences has remained unclear. Here, we quantified the interaction between full-length human Cn and NHE1-CnBD in distinct activation states using fluorescence anisotropy and quantitative size-exclusion…",
  "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."
}