Fig. 1: Cryo-EM structure of human ORC2–5.

a–c Cryo-EM density map of HsORC2–5 displayed in AAA+ view (a), WHD view (b), and side view (c). ORC subunits are color-coded and labeled. d, e Atomic models of HsORC2–5 (d) and DmORC (PDB: 4XGC) (e) displayed in AAA+ view. Domains are colored in the same color code as in a–c. f Schematic representation of the secondary structural elements of HsORC2-WHD. Secondary structural elements are labeled and colored in rainbow-mode. g, h Zoomed-in view of the boxed regions in d, e, showing the interaction between HsORC2-WHD and the AAA+ layer of the other subunits in HsORC2–5 (g) and DmORC (h). Secondary structure elements of HsORC2-WHD are labeled and colored, and HTH motif (α3–α4) are highlighted with transparent surface representation. For simplification, only the ISM motifs and other motifs (colored gray) interacting with HsORC2-WHD are displayed. ISM motifs are colored in the same color code as in d, e. ISM motifs without interaction with HsORC2-WHD are set transparent. Blue dashed circle shows the hollow DNA-binding central channel with a diameter of 10–14 Å in h. i, j Zoomed-in view of the boxed region in g showing the interaction between the turn loop of HsORC2-HTH motif and the AAA+ domains of HsORC4 and HsORC5. The electrostatic potential surface of HsORC4 and HsORC5 contacting HsORC2-HTH is displayed in i. Key residues involved in the interactions are labeled. k, l Similar to g, h, but with the view angle rotated 180°, the interaction between HsORC2-WHD and the WHD layer of the other subunits is shown in HsORC2–5 (k) and DmORC (l). For simplification, only the β-hairpin motifs are displayed and colored in the same color code as in d, e. β-hairpin motifs without interaction with HsORC2-WHD are set transparent. There is a rotation, ~120°, between the position of HsORC2-WHD in HsORC2–5 and DmOrc2-WHD in DmORC.