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Mode of Action (MoA)
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binds directly to the TIR (NADase) domain of the anti-phage defense protein SpbK, inhibiting its NADase activity and thereby preventing abortive infection.
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Evidence
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Nip (NADase inhibitor from phage) was identified as a phage-encoded counter-defense protein that inhibits the SpbK NADase defense system. Its activity was demonstrated through infection assays with wild-type Φ3T and a Δnip mutant. Deletion of nip from Φ3T (Φ3T Δnip) drastically reduced infectivity on B. subtilis strains expressing SpbK (ECO_0001038), whereas reintroduction of nip restored infectivity, confirming its necessity and sufficiency for counter-defense. Co-expression of nip in strains harboring both spbK and yonE abolished SpbK-dependent growth arrest and NAD⁺ depletion, demonstrating functional inhibition of NADase activity. Infection of spbK⁺ strains with Φ3T Δnip, but not with wild-type Φ3T, led to significant NAD⁺ depletion, further supporting this effect during infection. Co-immunoprecipitation experiments revealed that Nip binds directly to the TIR (NADase) domain of SpbK but not to its N-terminal domain. Additional immunoprecipitation assays showed formation of a tripartite complex among Nip, SpbK, and YonE, with Nip-SpbK interaction occurring independently of YonE. These data collectively demonstrate that Nip counteracts SpbK-mediated abortive infection by directly binding and inhibiting its enzymatic activity.
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MoA Category
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binds and inhibits host defence system
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Subtype(s) of the defence system(s) inhibited by the protein
Defence Subtype
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Bacillus subtilis SpbK
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Relevant publication(s)
DOI
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10.1371/journal.pgen.1011551
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Other components of the anti-defence system
Multicomponent System
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-
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Known structure in PDB
PDB ID
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-
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Genome(s) encoding the protein
Protein Source
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Phage Φ3T
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Defence system(s) inhibited by the protein
Defences
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SpbK
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