Fig. 2.

Cryo-EM structure of semi-attached OCCM. (A, Left) Cryo-EM 3D map viewed from the narrower, C-terminal tier. Subunits are individually colored. Orc1 has been omitted for clarity. (Inset, Right) ORC–DNA interaction outside the central channel. (B, Left) Side view of the 3D map. (Inset, Right) Orc2 WHD (shown in gray) occupies the gap between Orc1 and Orc2 in the ORC–DNA structure; this domain moves out (shown in beige) to accommodate Cdc6 binding in ORC–Cdc6–DNA. (C) The N-terminal view shows that Mcm3 WHD binds to the Orc2 WHD and the AAA+ domain of Cdc6 and Mcm7 WHD binds to the WDH of Cdc6 and the AAA+ domain of Orc1. (D) An open-book sketch showing that the binding interface for the Mcm3 and Mcm7 WHDs is not available in ORC–DNA and becomes available only when Cdc6 binds ORC–DNA. It also illustrates that the Cdt1–Mcm2-7 is largely flexible at the very first “anchoring” step.