Architecture of the cytoplasmic face of the human nuclear pore complex (NPC). (A) Cross-sectional view of the near-atomic composite structure of the human NPC generated by docking nucleoporin and nucleoporin complex crystal and single particle cryo-EM structures into an ∼12-Å cryo-ET map of the intact human NPC (Bley et al. 2022; Mosalaganti et al. 2022). The nuclear envelope is shown as a gray isosurface, the inner ring is displayed in cartoon representation uniformly colored pale blue, and the nuclear and cytoplasmic face structures are displayed in cartoon representation colored according to the legend. (B) Architecture of the cytoplasmic face of the human NPC (Bley et al. 2022). Flexibly attached NUP358 domains protrude into the cytoplasm. (C) Schematic representation of a single cytoplasmic face protomer, illustrating the attachment of a NUP358 pentameric bundle held together by interactions between oligomerization elements (OEs). Four NUP358NTD copies wrap around the tandem arranged Y-shaped CNC stalks, generating a binding site for a fifth copy. (D) Cartoon representations of crystal structures of NUP358 complexes: NUP358NTD (PDB ID 7MNL), NUP358ZnF7•Ran(GDP) (PDB ID 7MNU), NUP358RanBD-IV•Ran(GTP) (PDB ID 7MNZ) (Bley et al. 2022), NUP358E3•SUMO-RanGAP•UBC9 (PDB ID 1Z5S) (Reverter and Lima 2005), NUP358CTD (PDB ID 4I9Y) (Lin et al. 2013). (Figure adapted from Bley et al. 2022, with permission from the authors.)