Fig. 2: Reconstruction of a functional conformational landscape of APC/C–CDH1-mediated polyubiquitination using cryoDRGN.

a, PCA representation of the particle distribution in latent space with explained variance (EV) noted in parentheses. The first component captures the continuous conformational changes the APC/C undergoes in the ‘CRL down’ to ‘CRL up’ transition. Density for APC2, APC11 and CDH1 are shown at indicated points as green, blue and purple, respectively. b, 3D models generated using homogeneous 3D refinement of each set of major state particles. Density maps are colored by proximity to the subunit indicated as modeled using rigid body fitting. c,d, Left: UMAP representation of the particle distribution in latent space clustered using k-means (k = 500) clustering and then classified into the four major APC/C states present within the APC/C^CDH1–UBE2C (c) and APC/C^CDH1–UBE2C–UBE2S (d) datasets. Points denote cluster centers where volumes were generated. Right: subplots of particle distributions separated by major states. Particle distributions for each class are colored by their local density overlayed onto the particle distribution for the entire dataset (gray). e,f, Top: charts show distribution of particles across major states for the APC/C^CDH1–UBE2C (e) and APC/C^CDH1–UBE2C–UBE2S (f) datasets. Bottom: line graphs show change in relative fraction of each major state over time in the two datasets.