Prp8 rearrangements throughout the splicing cycle. (A) The four Prp8 domains (amino-terminal, Large, RNase H, and Jab) rearrange throughout the splicing cycle. All available spliceosome cryo-electron microscopy (cryo-EM) structures were aligned on the Prp8 Large domain and relative movements of the other domains are shown with a cartoon schematic. Although the amino-terminal domain moves only during the B to Bact transition, to clamp the 5′ exon, the RNase H and Jab1 domains move extensively between states. Thereby they contribute to the stabilization of exchanging spliceosome proteins (RNase H, Jab1) and movements of the branch helix (RNase H). See Figures 6 and 7. (B) Structural remodeling of the Prp8 α-finger throughout the splicing cycle. The Prp8 α-finger lies at the heart of the active site, where it changes its conformation to help organize the active site during multiple steps of splicing. See Figures 6 and 7.