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Mode of Action (MoA)
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bind and sequester the TIR-produced signaling molecules 3′cADPR and His-ADPR
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Evidence
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Lockin was identified as a broad-spectrum anti-Thoeris sponge family by infectivity assays showing that multiple Lockin proteins restored phage SBSphiJ propagation in cells expressing type I and/or type II Thoeris systems. Infected cells co-expressing Lockin and ThsB failed to accumulate 3′cADPR, as shown by NADase-based assays. Biochemical validation included size-exclusion chromatography (ECO_0000325) and HPLC (ECO_0001272) confirming direct binding and reversible sequestration of 3′cADPR by Lockin. Crystallography of LockinA with 3′cADPR revealed a homo-hexameric complex (ECO_0001171) with six deep inter-protomer pockets sequestering the signaling molecule. Mutations in pocket-coordinating residues K45 and K48 impaired anti-defense activity, confirming their role in nucleotide binding.
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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 cereus MSX-D12 type I Thoeris and Bacillus amyloliquefaciens Y2 type II Thoeris
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Relevant publication(s)
DOI
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10.1101/2025.07.12.664507
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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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Metagenomics data (IMG_VR ID: IMGVR_UViG_3300014204_000177)
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Defence system(s) inhibited by the protein
Defences
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Thoeris
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