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. Author manuscript; available in PMC: 2023 Mar 20.
Published in final edited form as: Mol Cell. 2023 Feb 16;83(5):746–758.e5. doi: 10.1016/j.molcel.2023.01.024

Figure 6. Model for type I-C Cascade-dsDNA activation and inhibition by Acrs.

Figure 6.

(I) The type I-C Cascade Cas8c has a minimal PAM-recognition requirement. (II) Cas8c N-term is stabilized upon dsDNA binding and responsible for the initial melting of the duplex. (III) Cas7 backbone stretches to accommodate the annealing of TS to crRNA. (IV) Cas8c and Cas11 subunits undergo conformational rotation to support NTS stabilization through an intriguing mechanism of NTS-base clamping between aromatic residues. (V) Once complete R-loop conformation has been established, Cas3c is recruited to degrade the foreign DNA. (VI) AcrIF2 crowds the Cas8c N-term PAM-recognition region and jams the vice-like Cas8c C terminus into a non-productive configuration. (VII) AcrIC4 makes specific contacts with Cas7.6 and Cas8c causing steric hindrance at the PAM-recognition site. This cartoon was created with Biorender.com.