Ligand-induced conformational changes of Cas9. The movie shows a series of conformational changes starting with a structure of Cas9 protein from Streptococcus pyogenes (SpCas9, PDB ID 4CMP) that transitions to the sgRNA-bound conformation (4ZT0), the ssDNA bound state (4008), PAM-bound state (4UN3), and finally to a complex that includes dsDNA + PAM (5F9R). Positions of the HNH and RuvC nuclease domains and their active sites are highlighted. The movie was created using ChimeraX (Protein Sci. 27, 14–25, 2018).