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Mode of Action (MoA)
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sequesters gcADPR
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Evidence
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Comparative genomics of closely related phages with differential sensitivity to the Thoeris defence system identified Tad2 as a factor conferring resistance. Deletion of tad2 rendered phages sensitive to Thoeris defence (ECO_0001038) and inserting tad2 into a sensitive phage conferred resistance.. Ectopic expression of tad2 (ECO_0000017) blocked Thoeris-mediated defence in bacterial cells. Biochemical evidence supports that Tad2 binds 1″–3′ gcADPR (KD ≈ 23.3 nM), preventing activation of the NADase effector ThsA. Crystal structure further supports sponge function (ECO_0005671).
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MoA Category
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degrades or sequesters molecules utilised by host defence systems
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Subtype(s) of the defence system(s) inhibited by the protein
Defence Subtype
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Bacillus subtilis type I Thoeris
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Relevant publication(s)
DOI
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10.1038/s41586-023-06869-w
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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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8SME
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Genome(s) encoding the protein
Protein Source
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Bacillus phage SPO1
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Defence system(s) inhibited by the protein
Defences
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Thoeris
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