Fig. 5: Updated model of step-wise assembly and activation of human ORC. | Cell Discovery

Fig. 5: Updated model of step-wise assembly and activation of human ORC.

From: Structural insight into the assembly and conformational activation of human origin recognition complex

Fig. 5

a ORC1 recognizes and binds to the initiation site through its N-terminal BAH domain or other DNA-binding elements. b Chromatin-anchored ORC1 recruits ORC2–5 to form a tightly inhibited conformation (HsORC1–5 State I). c ORC1–5 transits to another conformational state (HsORC1–5 State II), still autoinhibited, but to a less extent. d Intrinsic flexibility of ORC1–5 (with flexible ORC2-WHD and ORC1-AAA+, denoted by unfilled red and yellow ovals, respectively) permits the sampling of fully active conformation that is competent for DNA encirclement. e ORC1–5 encircles DNA using the canonical DNA-binding channel and is converted to a functionally active form ready for CDC6 association and subsequent helicase loading.

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