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Mode of Action (MoA)
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AlphaFold 3 predicts a high confidence interaction between helicase/endonuclease Cas3 (https://www.ncbi.nlm.nih.gov/protein/UEM35119.1) and AcrIC3 (ipTM = 0.91, pTM = 0.90) and a moderate confidence interaction between Cas2 (https://www.ncbi.nlm.nih.gov/protein/UEM35125.1) and AcrIC3 (ipTM = 0.7, pTM = 0.56).
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Evidence
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DMS3m phage was genetically engineered to carry the acrIC3 gene. This phage was then used to infect PAO1IC, a strain expressing the Type I-C CRISPR–Cas system from PaLML1 along with a crRNA targeting DMS3m. The engineered phage formed plaques on PAO1IC with an efficiency comparable to that on a non-targeting control strain, indicating strong anti-CRISPR activity. However, when Cas3 was fused to Cas8 — mimicking natural Cas3-Cas8 fusions to eliminate the normal recruitment interface — AcrIC3 no longer conferred protection, suggesting it normally blocks Cas3 recruitment to the Cascade complex. Binding it supported by computational structure modeling evidence (ECO_0006368).
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MoA Category
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binds and inhibits host defence system (putative)
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Subtype(s) of the defence system(s) inhibited by the protein
Defence Subtype
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Pseudomonas aeruginosa type I-C CRISPR-Cas system
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Relevant publication(s)
DOI
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10.1093/nar/gkab006
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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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MGE in Pseudomonas aeruginosa
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Defence system(s) inhibited by the protein
Defences
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CRISPR-Cas
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