{
  "abstract": "The cardiac thin filament (cTF) regulates contraction through Ca2+ binding to, and release from, cardiac troponin C (cTnC), yet how sarcomeric accessory proteins influence these kinetics remains incompletely understood. Cardiac myosin-binding protein C (cMyBP-C) N-terminal domains interact with the thin filament and are regulated by PKA-mediated phosphorylation. To determine whether cMyBP-C alters thin filament Ca2+ exchange kinetics, we performed stopped-flow measurements using 2-(4´-(iodoacetamido)anilino)naphthalene-6-sulfonic acid-labeled cTnC in reconstituted cTFs. The N-terminal fragments C0-C2 and C1-C2 slowed Ca2+ dissociation in a concentration-dependent manner, whereas C0-C1 produced only a modest effect. PKA-mediated phosphorylation markedly attenuated the slowing by C0-C2 and C1-C2. Thus, N-terminal domain composition and phosphorylation state strongly influence cMyBP-C-mediated regulation of thin filament Ca2+ dissociation. In contrast, the tested cMyBP-C fragments did not alter Ca2+ association kinetics or Ca2+ dissociation from isolated troponin. Cosedimentation measurements further showed that differences in kinetic effects were not explained solely by differences in thin filament occupancy. Together, these results demonstrate that cMyBP-C N-terminal fragments selectively modulate Ca2+ dissociation from cTnC in myosin-free reconstituted cTFs. The absence of an effect on isolated troponin is consistent with regulation involving additional thin filament components, including actin and/or tropomyosin, although tropomyosin-dependent and -independent mechanisms remain possible. This work identifies a previously unrecognized effect of cMyBP-C N-terminal domains on cTnC Ca2+ dissociation in the cTF.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cellular & Molecular Medicine, University of Arizona, Tucson, Arizona, USA",
    "Department of Biomedical Engineering, University of Arizona, Tucson, Arizona, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Garrett T. Hauck"
    },
    {
      "affs": [
        0
      ],
      "name": "Fiona L. Wong"
    },
    {
      "affs": [
        1
      ],
      "name": "Matthew M. Klass"
    },
    {
      "affs": [
        0
      ],
      "name": "Rhye-Samuel Kanassatega"
    },
    {
      "affs": [
        0
      ],
      "name": "Victoria C. Lepak"
    },
    {
      "affs": [
        0
      ],
      "name": "Thomas A. Bunch"
    },
    {
      "affs": [
        1
      ],
      "name": "Jil C. Tardiff"
    },
    {
      "affs": [
        0
      ],
      "name": "Brett A. Colson"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aey15yztrhthe.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jbc.2026.113601",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696821/",
  "id": "aey15yztrhthe",
  "issns": [
    "0021-9258",
    "1083-351X"
  ],
  "landing_url": "https://doi.org/10.1016/j.jbc.2026.113601",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "JBC Communication"
    ],
    [
      "openalex",
      "2705|Cardiomyopathy and Myosin Studies"
    ]
  ],
  "openalex": "W7214126975",
  "pdf_url": null,
  "pmcid": "PMC13696821",
  "pmid": "42778103",
  "published": "2026-09-23",
  "publisher": "American Society for Biochemistry and Molecular Biology",
  "ris": "https://research.draconitic.com/paper/aey15yztrhthe.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:06Z",
      "native_id": "PMC13696821",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jbc.2026.113601"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiomyopathy and Myosin Studies",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Myosin-binding protein C N-terminal domains slow Ca2+ dissociation from cardiac thin filaments",
  "title_text": "Myosin-binding protein C N-terminal domains slow Ca2+ dissociation from cardiac thin filaments",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:05Z",
  "url": "https://research.draconitic.com/paper/aey15yztrhthe",
  "venue": "The Journal of Biological Chemistry",
  "versions": []
}