Fig. 1: Phage-derived Acrs targeting type II CRISPR–Cas9, type V CRISPR–Cas12a and type VI CRISPR–Cas13a. | Nature Chemical Biology

Fig. 1: Phage-derived Acrs targeting type II CRISPR–Cas9, type V CRISPR–Cas12a and type VI CRISPR–Cas13a.

From: De novo design of potent CRISPR–Cas13 inhibitors

Fig. 1: Phage-derived Acrs targeting type II CRISPR–Cas9, type V CRISPR–Cas12a and type VI CRISPR–Cas13a.

Acr proteins use diverse mechanisms to inhibit CRISPR–Cas systems through interactions with the nuclease or recognition lobes. Targeting type II (Cas9), AcrIIA4 (PDB 5XN4)57 and AcrIIC1 (PDB 5VGB)40 block DNA target recognition and the HNH nuclease, respectively. Targeting type V (Cas12a), AcrVA4 (PDB 6NMA)58 allosterically inhibits DNA binding and AcrVA1 (PDB 6NMD)58 cleaves the crRNA to prevent target DNA recognition. Targeting type VI (Cas13), AcrVIA1 (PDB 6VRB)14 inhibits RNA cleavage by blocking aRNA recognition. No inhibitors have been described that block the highly conserved HEPN domain of type VI CRISPR–Cas13. PAM, protospacer-adjacent motif; gRNA, guide RNA; crRNA, CRISPR RNA; aRNA, activator RNA.

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