{
  "abstract": "PAS domains often bind cofactors, whereas related Cache domains are thought to function exclusively as ligand-binding modules. We identify and characterize a large family of Cache domains containing covalently bound c-type heme. Sequence, phylogenetic and structual analysis of the DUF3365/Tll0287 family reveals conservation of a canonical CXXCH heme-binding motif, establishing c-type heme binding as a defining feature of this family. Despite previous annotation as PAS-like, these proteins share a distinct heme-binding insertion into a pre-existing Cache scaffold, representing the first documented recruitment of an intact cofactor-binding motif into a bacterial sensor domain. Domain architecture further divides the family into two subclasses: one exhibiting fusions to signaling domains and another comprised of standalone proteins. Spectroscopic analyses indicate that a representative signaling protein acts as a nitric oxide sensor, whereas a stand-alone representative exhibits redox-related properties and weak nitric oxide binding. These findings expand the functional repertoire of Cache domains and reveal a mechanism for the evolution of bacterial sensory systems.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Maithili Deshpande",
      "orcid": "0000-0003-3556-1169"
    },
    {
      "name": "Jiawei Xing",
      "orcid": "0000-0002-7691-1180"
    },
    {
      "name": "Vadim M. Gumerov",
      "orcid": "0000-0003-1670-7679"
    },
    {
      "name": "Robert Dunleavy"
    },
    {
      "name": "Herbert Castillo",
      "orcid": "0000-0002-3751-7463"
    },
    {
      "name": "Brian R. Crane",
      "orcid": "0000-0001-8234-9991"
    },
    {
      "name": "Igor B. Zhulin",
      "orcid": "0000-0002-6708-5323"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cqph7mksfj0k1.bib",
  "cited_by": 0,
  "doi": "10.1038/s42003-026-11299-1",
  "fulltext_url": null,
  "id": "cqph7mksfj0k1",
  "issns": [
    "2399-3642"
  ],
  "landing_url": "https://www.nature.com/articles/s42003-026-11299-1",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/cqph7mksfj0k1.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:50Z",
      "native_id": "10.1038/s42003-026-11299-1",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s42003-026-11299-1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:2399-3642",
      "subfield": "general"
    }
  ],
  "title": "A dichotomous family of Cache domain proteins evolved through c-type heme acquisition",
  "title_text": "A dichotomous family of Cache domain proteins evolved through c-type heme acquisition",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:20:53Z",
  "url": "https://research.draconitic.com/paper/cqph7mksfj0k1",
  "venue": "Communications Biology",
  "versions": []
}