7JK4

Structure of Drosophila ORC bound to AT-rich DNA and Cdc6

Summary for 7JK4

• Entry DOI: 10.2210/pdb7jk4/pdb
• EMDB information: 22329 22330 22359 22360 22361 22362 22363
• Descriptor: Origin recognition complex subunit 2, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (11 entities in total)
• Functional Keywords: origin recognition complex, dna replication initiation, replication, replication-dna complex, replication/dna
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 9
• Total formula weight: 426821.15

Authors

Schmidt, J.M.,Bleichert, F. (deposition date: 2020-07-27, release date: 2020-09-09, Last modification date: 2024-03-06)

Primary citation

Schmidt, J.M.,Bleichert, F.
Structural mechanism for replication origin binding and remodeling by a metazoan origin recognition complex and its co-loader Cdc6.
Nat Commun, 11:4263-4263, 2020

PubMed Abstract: Eukaryotic DNA replication initiation relies on the origin recognition complex (ORC), a DNA-binding ATPase that loads the Mcm2-7 replicative helicase onto replication origins. Here, we report cryo-electron microscopy (cryo-EM) structures of DNA-bound Drosophila ORC with and without the co-loader Cdc6. These structures reveal that Orc1 and Orc4 constitute the primary DNA binding site in the ORC ring and cooperate with the winged-helix domains to stabilize DNA bending. A loop region near the catalytic Walker B motif of Orc1 directly contacts DNA, allosterically coupling DNA binding to ORC's ATPase site. Correlating structural and biochemical data show that DNA sequence modulates DNA binding and remodeling by ORC, and that DNA bending promotes Mcm2-7 loading in vitro. Together, these findings explain the distinct DNA sequence-dependencies of metazoan and S. cerevisiae initiators in origin recognition and support a model in which DNA geometry and bendability contribute to Mcm2-7 loading site selection in metazoans.

PubMed: 32848132
DOI: 10.1038/s41467-020-18067-7

Experimental method

ELECTRON MICROSCOPY (3.4 Å)