Figure 4.
Model for CasA L1-dependent non-self target recognition by Cascade. (a) CasA L1-dependent non-specific binding localizes Cascade on target DNA. (b) Upon encountering a PAM sequence, CasA L1 binding destabilizes the duplex. (c) In the presence of a proto-spacer, L1-mediated PAM destabilization facilities strand invasion by the seed sequence. (d) Upon duplex nucleation at the seed, full spacer—proto-spacer binding can be completed. CasA is shown as a yellow-green triangle, CasB1-2 as horizontal ellipses, CasC1-6 as squares, CasD as a circle, and CasE as a vertical ellipse. The PAM is shown in red, the seed in blue, and the rest of the crRNA and proto-spacer in pink.