|
Mode of Action (MoA)
|
acts as a dsDNA mimic that blocks target recognition by competing for a critical DNA-binding site on Cas7 and Cas8.
|
|
Evidence
|
AcrIF2* was expressed from a DMS3m phage and tested on PAO1IC (Type I-C) and PA14 (Type I-F). The engineered phage formed plaques efficiently on both hosts (EOP ≈ 1), demonstrating dual inhibition of I-C and I-F systems. However, when both CRISPR systems were co-expressed in the host (one targeting, one non-targeting), AcrIF2*-phage infectivity dropped ~100–1000-fold at low MOI, suggesting a competition effect between the two systems for the inhibitor. Structural data and mutagenesis of eight acidic residues (to alanine) showed that AcrIF2* can tolerate major surface changes and still function, but loses robustness under competition. In CRISPRi assays, it fully rescued transcription, confirming it acts by blocking Cascade DNA binding. Its function is consistent with DNA mimicry.
|
|
MoA Category
|
binds and inhibits host defence system
|
|
Subtype(s) of the defence system(s) inhibited by the protein
Defence Subtype
|
Pseudomonas aeruginosa type I-F and I-C CRISPR-Cas system
|
|
Relevant publication(s)
DOI
|
10.1093/nar/gkab006
|
|
Other components of the anti-defence system
Multicomponent System
|
-
|
|
Known structure in PDB
PDB ID
|
5uz9_J
|
|
Genome(s) encoding the protein
Protein Source
|
Pseudomonas aeruginosa phages D3112
|
|
Defence system(s) inhibited by the protein
Defences
|
CRISPR-Cas
|