Figure 8.
A model of conformation states of Cascade at different target variants. The Cse1 subunit is predominantly in the open state for the –1 and +1 substitutions resulting in a weak (semi-locked) R-loop that is not able to support efficient Cas3 recruitment. For other seed substitutions the locking strength and the ability to recruit Cas3 increase with increasing distance from the PAM, reaching the WT level for +4 substitution (suggesting a closed WT-like Cse1 conformation that readily recruits Cas3).