{
  "abstract": "TIR domains are found in diverse immune signaling proteins and, in several systems, function as NAD+-cleaving enzymes causing or signaling cell death. In plants, TIR domains occur as effector domains in TNL immune receptors, where they are coupled to a central STAND ATPase and a C-terminal repeat domain. Here, we identify TeTIR (TEP1 extended TIR), a previously unrecognized family of TIR-like domains associated with NACHT-type ATPases and C-terminal WD40 or TPR repeat domains. The TeTIR domain of human TEP1 exhibits robust NADase activity comparable to SARM1-TIR, making TEP1 the only other NADase-active TIR-like protein identified in mammals. NADase activity is conserved in TEP1 homologs from diverse eukaryotes. The crystal structure of TEP1 TeTIR reveals an extended TIR-like fold with additional secondary-structure elements and a distinctive RWG-containing loop. Molecular dynamics simulations indicate that the catalytic glutamate contributes to catalysis and the conformational equilibrium of the active-site region, promoting formation of a substrate-accessible state. Structure-guided mutagenesis identifies conserved residues contributing to NAD+ recognition and catalysis, including features distinct from canonical TIR NADases. Expression of isolated TEP1 TeTIR causes NAD+ depletion and cell death in a catalytic-glutamate-dependent manner. TeTIRs thus define a distinct family of animal TIR-like NADases embedded in NACHT-type STAND architectures.",
  "abstract_shown": true,
  "affiliations": [
    "University of Cologne"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "J. Hornebeck"
    },
    {
      "name": "R. Ibragimov"
    },
    {
      "name": "N. Oelerich"
    },
    {
      "name": "P. Pfad"
    },
    {
      "name": "J. Jirschitzka"
    },
    {
      "name": "J. M. Gebauer"
    },
    {
      "name": "U. Baumann"
    },
    {
      "name": "T. Hermanns"
    },
    {
      "affs": [
        0
      ],
      "name": "K. Hofmann"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0v8h7zj0pamws.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.21.753143",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753143v1.full",
  "id": "0v8h7zj0pamws",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753143v1",
  "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",
      "biochemistry"
    ],
    [
      "openalex",
      "2403|Immune Response and Inflammation"
    ]
  ],
  "openalex": "W7213972774",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753143v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0v8h7zj0pamws.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:43Z",
      "native_id": "10.64898/2026.09.21.753143",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753143v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune Response and Inflammation",
      "subfield": "immunology"
    }
  ],
  "title": "TeTIR domains define a new class of animal TIR-like NADase effectors in STAND proteins",
  "title_text": "TeTIR domains define a new class of animal TIR-like NADase effectors in STAND proteins",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:43Z",
  "url": "https://research.draconitic.com/paper/0v8h7zj0pamws",
  "venue": "bioRxiv",
  "versions": []
}