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Mode of Action (MoA)
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AlphaFold 3 predicts a high confidence interaction between Cas9 (https://www.ncbi.nlm.nih.gov/protein/QHB64844.1) and AcrIIA26 (ipTM = 0.87, pTM = 0.79)
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Evidence
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Expression of AcrIIA26 in E. coli prevented Cas9-mediated plasmid interference, particularly with SpyCas9 (ECO_0000017). AcrIIA26 was cloned and tested in interference assays, which showed full protection. In vitro cleavage reactions showed that AcrIIA26 blocked RNP–DNA binding. EMSAs confirmed prevention of RNP-DNA complex formation (ECO_0001807). In human cells, co-transfection of AcrIIA26 with SpyCas9 led to near-complete loss of indel formation, supporting a DNA-binding inhibition mechanism. 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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Streptococcus thermophilus and Streptococcus pyogenes type II-A CRISPR-Cas
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Relevant publication(s)
DOI
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10.1093/nar/gkac099
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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 Streptococcus sp.
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Defence system(s) inhibited by the protein
Defences
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CRISPR-Cas
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