Fig. 2: Heterogeneity analysis on the pre-catalytic spliceosome (EMPIAR-10180).

a, UMAP visualization of the 12-dimensional latent space of all particles encoded by OPUS-DSD. Solid black dots represent the cluster centers for labeled classes. b, Conformations with major compositional heterogeneities determined using OPUS-DSD. The density maps were generated by the decoder of OPUS-DSD with the corresponding class centers shown in a. Class 12 is the expected structure of the pre-catalytic spliceosome, class 10 is a complete structure with the U2 core, class 18 only has the core, and class 14 lacks the SF3b subcomplex. c, Open and closed conformations of the spliceosome generated along the PC1 of the latent space. The open and closed conformations were generated at the PC1 with an amplitude of −1.1 and 1.0, respectively. The superposition shows the displacement of SF3b and helicase between these two conformations as indicated by the green arrows. The yellow dashed ellipses highlight the occupancy differences of a chain between helicase and SF3b in different conformations. The yellow dashed circles mark the domain in SF3b that connects to this chain. All maps were contoured at the same level and visualized using ChimeraX³⁴.