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Mode of Action (MoA)
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functions as an acetyltransferase and modifies Cas12a.
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Evidence
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AcrVA5 was discovered within the same GF59 genomic fragment as AcrVA4, identified as GF59 candidate 3. The TXTL system includes plasmids that encode fluorescent proteins (GFP and RFP). Guide RNAs (gRNAs) are also included that direct Cas12a to specifically target and cleave the reporter plasmids. TXTL screening showed elevated fluorescence of both reporters, suggesting CRISPR inhibition. In purified protein assays, AcrVA5 inhibited dsDNA cleavage by MbCas12a and LbCas12a, but not AsCas12a, and showed no inhibition of MbCas12a from strain 58069. In mammalian cells, AcrVA5 inhibited LbCas12a-mediated genome editing but did not impact AsCas12a or SpyCas9. These findings support AcrVA5 as a selective inhibitor of certain Cas12a orthologs.
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MoA Category
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adds a post-translational modification and deactivates bacterial defence
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Subtype(s) of the defence system(s) inhibited by the protein
Defence Subtype
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Moraxella bovoculi and Lachnospiraceae bacterium type V-A CRISPR-Cas
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Relevant publication(s)
DOI
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10.1126/science.aau5138
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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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6IUF_A
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Genome(s) encoding the protein
Protein Source
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MGE in Moraxella bovoculi 58069
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Defence system(s) inhibited by the protein
Defences
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CRISPR-Cas
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