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Mode of Action (MoA)
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binds to Cas9, blocking the PAM recognition sites.
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Evidence
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AcrIIA15 was also identified by guilt-by-association with genes adjacent to the same aca-like region. AcrIIA15 was cloned and expressed in TXTL, where it restored GFP expression in the presence of SauCas9 (ECO_0000017). In vitro, AcrIIA15 inhibited SauCas9 cleavage only when added prior to sgRNA, indicating it blocks RNP formation by binding Cas9 before guide RNA association. RNA EMSA confirmed it disrupted RNP formation, and DNA EMSA showed inhibition of target binding if added early (ECO_0001807). The C-terminal domain alone retained inhibitory activity, while the N-terminal HTH domain was dispensable for Cas9 inhibition.
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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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Staphylococcus aureus type II-A CRISPR-Cas
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Relevant publication(s)
DOI
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10.1073/pnas.1917668117
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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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8JFO_B
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Genome(s) encoding the protein
Protein Source
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MGE in Staphylococcus delphini
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Defence system(s) inhibited by the protein
Defences
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CRISPR-Cas
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