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Mode of Action (MoA)
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interacts with both the Cas7c and Cas8c subunits and inhibits dsDNA binding by acting as a negatively charged structural blockade at the PAM recognition site.
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Evidence
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Phage-encoded acrIC4 was introduced into DMS3m and tested on PAO1IC. The phage regained full infectivity (EOP ≈ 1), indicating strong inhibition of Type I-C immunity. AcrIC4 also relieved transcriptional repression in a CRISPRi assay, confirming it blocks DNA binding by Cascade. AcrIC4 activity was unaffected by Cas3–Cas8 tethering. Cryo-EM structure of the type I-C Cascade bound to AcrIC4 (ECO_0006181) revealed how AcrIC4 inhibits DNA targeting, specifically binding at the PAM recognition site, forming an electrostatic and steric blockade that prevents the Cascade complex from engaging with its DNA target.
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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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Pseudomonas aeruginosa type I-C CRISPR-Cas system
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Relevant publication(s)
DOI
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10.1093/nar/gkab006,
10.1016/j.molcel.2023.01.024
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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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8DFO_M
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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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