Summary information and primary citation
- PDB-id
- 6f0l; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- hydrolase
- Method
- cryo-EM (4.77 Å)
- Summary
- S. cerevisiae mcm double hexamer bound to duplex DNA
- Reference
- Abid Ali F, Douglas ME, Locke J, Pye VE, Nans A, Diffley JFX, Costa A (2017): "Cryo-EM structure of a licensed DNA replication origin." Nat Commun, 8, 2241. doi: 10.1038/s41467-017-02389-0.
- Abstract
- Eukaryotic origins of replication are licensed upon loading of the MCM helicase motor onto DNA. ATP hydrolysis by MCM is required for loading and the post-catalytic MCM is an inactive double hexamer that encircles duplex DNA. Origin firing depends on MCM engagement of Cdc45 and GINS to form the CMG holo-helicase. CMG assembly requires several steps including MCM phosphorylation by DDK. To understand origin activation, here we have determined the cryo-EM structures of DNA-bound MCM, either unmodified or phosphorylated, and visualize a phospho-dependent MCM element likely important for Cdc45 recruitment. MCM pore loops touch both the Watson and Crick strands, constraining duplex DNA in a bent configuration. By comparing our new MCM-DNA structure with the structure of CMG-DNA, we suggest how the conformational transition from the loaded, post-catalytic MCM to CMG might promote DNA untwisting and melting at the onset of replication.
