TraitMech

TraitMech › GENOMICS

Clover system

traitmech:000415 · CLASS · PROPOSED

A phage defense system in which an organism possesses a Clover anti-phage system whose CloA deoxynucleoside triphosphohydrolase dynamically responds to an activating phage cue and to a CloB-produced inhibitory p3diT nucleotide signal to coordinate nucleotide-pool disruption during antiviral immunity.

Trait evidence (5)

  • DOI:10.1038/s41586-026-10135-0
    Here we identify Clover, a bacterial anti-phage defence system that overcomes this trade-off by encoding a deoxynucleoside triphosphohydrolase enzyme (CloA) that dynamically responds to both an activating phage cue and an inhibitory nucleotide immune signal produced by a partnering regulatory enzyme (CloB).

    Yu and Kranzusch define Clover as a bacterial anti-phage defence system encoding CloA and CloB.

  • DOI:10.1038/s41586-026-10135-0
    Analysis of phage restriction by Clover in cells and reconstitution of enzymatic function in vitro demonstrate that CloA is a dGTPase that responds to viral enzymes that increase cellular levels of dTTP.

    Yu and Kranzusch support CloA as a Clover dGTPase that responds to viral enzymes that increase cellular dTTP.

  • DOI:10.1038/s41586-026-10135-0
    To restrain CloA activation in the absence of infection, we show that CloB synthesizes a dTTP-related inhibitory nucleotide signal, p3diT

    Yu and Kranzusch support CloB synthesis of the inhibitory p3diT nucleotide signal.

  • DOI:10.1038/s41586-026-10135-0
    Cryo-electron microscopy structures of CloA in activated and suppressed states reveal how dTTP and p3diT control distinct allosteric sites and regulate effector function.

    Yu and Kranzusch resolve activated and suppressed CloA states controlled by dTTP and p3diT.

  • https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
    | Clover | 10\.1038/s41586-026-10135-0 | Nucleotide signals coordinate activation and inhibition of bacterial immunity |

    The pinned DefenseFinder article registry maps the named Clover system to the Yu and Kranzusch nucleotide-signal anti-phage-defense paper. The pinned HMM inventory and rules table do not list Clover, so this row is name-to-paper evidence rather than model-component evidence.

Clover coordinates CloA activation and inhibition

Conservative sketch linking a Clover locus to p3diT-gated CloA dGTPase activity, regulation of antiviral immunity, and Clover system possession.

NONMECHANISTIC · The graph captures Clover at the experimentally supported CloA/CloB dGTPase-regulation level without asserting exact native host breadth, full sensitive-phage breadth, profile-to-component mappings, or a DefenseFinder detection rule absent from the pinned model files.

Clover coordinates CloA activation and inhibition Interactive directed graph showing evidence-backed causal relationships for Clover system.

Edge evidence

  • Clover locus enables CloA dGTPase activation RO:0002327

    A Clover locus encodes the CloA dGTPase that responds to viral enzymes increasing cellular dTTP.

    • DOI:10.1038/s41586-026-10135-0 Here we identify Clover, a bacterial anti-phage defence system that overcomes this trade-off by encoding a deoxynucleoside triphosphohydrolase enzyme (CloA) that dynamically responds to both an activating phage cue and an inhibitory nucleotide immune signal produced by a partnering regulatory enzyme (CloB). Yu and Kranzusch identify Clover as the system encoding CloA and CloB.
    • DOI:10.1038/s41586-026-10135-0 Analysis of phage restriction by Clover in cells and reconstitution of enzymatic function in vitro demonstrate that CloA is a dGTPase that responds to viral enzymes that increase cellular levels of dTTP. Yu and Kranzusch connect Clover to dTTP-responsive CloA dGTPase activity.
  • Clover locus enables CloB p3diT synthesis RO:0002327

    A Clover locus encodes CloB, which synthesizes the inhibitory p3diT signal.

    • DOI:10.1038/s41586-026-10135-0 To restrain CloA activation in the absence of infection, we show that CloB synthesizes a dTTP-related inhibitory nucleotide signal, p3diT Yu and Kranzusch connect CloB to p3diT synthesis.
  • CloB p3diT synthesis negatively regulates CloA dGTPase activation RO:0002212

    The CloB-produced p3diT nucleotide signal binds CloA and suppresses CloA activation.

    • DOI:10.1038/s41586-026-10135-0 To restrain CloA activation in the absence of infection, we show that CloB synthesizes a dTTP-related inhibitory nucleotide signal, p3diT Yu and Kranzusch support p3diT-dependent suppression of CloA activation.
  • CloA dGTPase activation confers Clover system METPO:2007700

    Regulated CloA effector activity realizes Clover antiviral immunity.

    • DOI:10.1038/s41586-026-10135-0 Our results define how nucleotide signals coordinate both activation and inhibition of antiviral immunity Yu and Kranzusch frame nucleotide-mediated CloA activation and inhibition as coordinated antiviral immunity.
    • DOI:10.1038/s41586-026-10135-0 Cryo-electron microscopy structures of CloA in activated and suppressed states reveal how dTTP and p3diT control distinct allosteric sites and regulate effector function. Yu and Kranzusch show that dTTP and p3diT regulate Clover effector function through distinct CloA sites.
  • Clover system is a phage defense system rdfs:subClassOf

    Clover system possession is a phage-defense-system trait.

    • DOI:10.1038/s41586-026-10135-0 Here we identify Clover, a bacterial anti-phage defence system that overcomes this trade-off by encoding a deoxynucleoside triphosphohydrolase enzyme (CloA) that dynamically responds to both an activating phage cue and an inhibitory nucleotide immune signal produced by a partnering regulatory enzyme (CloB). Yu and Kranzusch define Clover as a bacterial anti-phage defence system.
    • https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md | Clover | 10\.1038/s41586-026-10135-0 | Nucleotide signals coordinate activation and inhibition of bacterial immunity | The pinned DefenseFinder article registry maps the named Clover system to the Yu and Kranzusch nucleotide-signal anti-phage-defense paper. The pinned HMM inventory and rules table do not list Clover, so this row is name-to-paper evidence rather than model-component evidence.

Provenance

Identifier source
TraitMech local identifier
Definition source
DOI:10.1038/s41586-026-10135-0

Parent traits (1)

Synonyms (1)

  • Clover EXACT_SYNONYM · DOI:10.1038/s41586-026-10135-0

kg-microbe context

No kg-microbe node embedding matched this record in the 2026-04-25 deepwalk.

Discussions and Knowledge Gaps (1)

Open questions attached to this trait. Seeded by just knowledge-gap-scan and curated; see the corpus-wide index.

Resolve Clover native host breadth, sensitive-phage breadth, profile-to-component coverage, and DefenseFinder HMM/rules coverage before minting narrower Clover mechanism children.

KNOWLEDGE GAP OPEN clover-defensefinder-model-gap · raised by codex · 2026-09-27

Attached to causal_graphs#clover_dttp_p3dit_regulated_dgtpase

Yu and Kranzusch support Clover as a bacterial anti-phage defence system whose CloA dGTPase is activated and suppressed by nucleotide signals, while the pinned DefenseFinder article registry names a Clover system. The pinned DefenseFinder HMM inventory and rules table have no Clover rows, and the evidence does not yet resolve native host breadth, full target-phage breadth, or profile-to-activity modeling.

Evidence

Curation history

  1. · MINTED_TRAITMECH_ID · codex

    Minted Clover system as a DOI-backed GENOMICS TraitRecord under phage defense system after an ignored-and-hidden duplicate review found no exact live TraitMech, METPO, history, or prior proposal record; kept the graph at CloA/CloB dGTPase-regulation level because the pinned DefenseFinder article row is not backed by pinned HMM or rules rows; the replacement placeholder is reserved in proposals/metpo_traitmech_v292.

  2. · REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP · codex

    Reviewed Clover system during canonical-example issue 444 enforcement and left canonical_examples empty because the sources support cloned Salmonella enterica and Escherichia coli operon expression in phage-challenge assays plus a DefenseFinder article-registry system name, but not a direct native microbial isolate exemplar with experimentally verified endogenous Clover activity. No paid research was used.