{
  "abstract": "Brain-type creatine kinase (CK-BB) buffers local ATP demand through reversible phosphotransfer between ATP and phosphocreatine, yet how this soluble metabolic enzyme engages membrane compartments is unknown. Here, we combine fluorescence microscopy, DEER spectroscopy, hydrogen-deuterium exchange and native mass spectrometry, DEER- and AlphaFold-guided modeling, and long-timescale molecular dynamics to define the pH- and substrate-regulated conformational landscape governing CK-BB membrane association. Acidification promotes curvature-sensitive membrane binding and redistributes endogenous and recombinant CK-BB from diffuse cytosolic pools to punctate vesicular structures and membrane ruffles. Substrates independently promote curvature-sensitive association at neutral pH. DEER and modeling reveal an asymmetric dimer in which the convex surface remains restrained, whereas the concave catalytic-regulatory surface samples pH- and substrate-dependent intermediates. We identify progressive dimer opening as a novel regulatory mechanism whereby acidification and substrate binding increase dynamics across the convex surface and N-terminal dimer interface, generating membrane-competent conformations that facilitate curvature sensing and membrane association. Substrate binding buffers acid-induced deprotection while preserving dynamics near the His191/Ser199 regulatory interface. These findings establish CK-BB as a previously unrecognized curvature-sensitive metabolic enzyme and define dimer dynamics as a molecular switch coupling protonation and substrate occupancy to curved-membrane recognition and localized ATP regeneration, with potential relevance to neurodegeneration and cellular stress.",
  "abstract_shown": true,
  "affiliations": [
    "Saint Louis University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "S. Gies"
    },
    {
      "name": "N. K. McLaughlin"
    },
    {
      "name": "O. H. Kou"
    },
    {
      "name": "A. Shubbar"
    },
    {
      "name": "C. Kong"
    },
    {
      "name": "T. Wu"
    },
    {
      "name": "S. Khan"
    },
    {
      "name": "A. Ustione"
    },
    {
      "name": "I. Miller"
    },
    {
      "name": "D. W. Piston"
    },
    {
      "name": "M. Moradi"
    },
    {
      "name": "M. L. Gross"
    },
    {
      "name": "W. F. Zeno"
    },
    {
      "affs": [
        0
      ],
      "name": "R. Dastvan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/99cfe458krd6s.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.04.742861",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.04.742861v2.full",
  "id": "99cfe458krd6s",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.04.742861v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7202044142",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.04.742861v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/99cfe458krd6s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:49Z",
      "native_id": "10.64898/2026.08.04.742861",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.04.742861v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Dimer opening enables brain-type creatine kinase to sense membrane curvature",
  "title_text": "Dimer opening enables brain-type creatine kinase to sense membrane curvature",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:49Z",
  "url": "https://research.draconitic.com/paper/99cfe458krd6s",
  "venue": "bioRxiv",
  "versions": []
}