FIGURE 5.

Binding site of ligand ISRIB in cryoEM structures 6EZO and 6CAJ. The coloring of subunits was kept consistent with Figure 1. The ligand (depicted as brown/orange sticks on structures 6EZO/6CAJ) binds at the tetrameric interface formed by the two subunits eIF2Bβ (magenta ribbon) and two eIF2Bδ (cyan ribbon). Figures (a) and (b) show binding site residues located 4 Å near ligand ISRIB (note: cryoEM structures 6EZO and 6CAJ have missing side‐chains for some residues), whereas figures (c) and (d) depict the locations of eIF2B mutations discussed and classified in this article (see Table S3). The mutated residues are shown as spheres and are colored by severity type