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Cascade (CRISPR-associated complex for antiviral defense) is a 405 kDa CRISPR RNA-guided surveillance complex that defends Esherichia coli against viral attack. Structures of Cascade determined using cryo-electron microscopy revealed a sea-horse-shaped architecture that undergoes a conformational rearrangement upon target binding, which may serve 5 as a signal for recruiting the trans-acting nuclease called Cas3 . However, the 8-9 Å resolution EM structures left many unanswered questions about Cascade assembly and the mechanics of DNA targeting. This particular model is the Cascade bound to ssDNA (red).