Fig. 5: Sequential disassembly of ORC-Cdc6 and structure of ORC-Cdc6/MCM connectivity in OC1MMcm5RA.
From: Unidirectional MCM translocation away from ORC drives origin licensing
a In ATPγS-OCCM (top left), the Orc1-Cdc6 and Orc4-Orc1 ATPase sites are ATPγS-engaged and visit a stable form that favours ATP binding. Orc5-4 and Orc3-5 sites are also bound to ATPγS. In OCCMMcm2RA (top right), Cdc6 (cryo-EM density) is flexible and ATP can only be observed in the Orc4-Orc1, Orc5-4 and Orc3-5 nucleotide-binding sites. In OC1MMcm5RA (bottom), Orc1 (cryo-EM density) is flexible and ATP can only be observed in the Orc5-4 and Orc3-5 sites. b Side view of the conformer 2 OC1MMcm5RA structure highlights changes in ORC-MCM connectivity compared to OCCMMcm2RA. The Mcm7 WHD domain, previously engaged to Orc1, becomes disordered and a new contact is created between the Mcm5 WHD domain and the Orc3 WHD, which could not be detected in OCCMMcm2RA. c MCM ATPase view shows that the Mcm2-5 gate remains closed in OC1MMcm5RA. ADP is bound at four inter-subunit sites.
