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7MCA

Structure of the S. cerevisiae origin recognition complex bound to the replication initiator Cdc6 and the ARS1 origin DNA.

Summary for 7MCA
Entry DOI10.2210/pdb7mca/pdb
EMDB information23755 23818
DescriptorOrigin recognition complex subunit 1, MAGNESIUM ION, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, ... (11 entities in total)
Functional Keywordsreplication initiation, replication
Biological sourceSaccharomyces cerevisiae (Baker's yeast)
More
Total number of polymer chains9
Total formula weight527256.28
Authors
Feng, X.,Li, H. (deposition date: 2021-04-01, release date: 2021-06-02, Last modification date: 2024-05-29)
Primary citationFeng, X.,Noguchi, Y.,Barbon, M.,Stillman, B.,Speck, C.,Li, H.
The structure of ORC-Cdc6 on an origin DNA reveals the mechanism of ORC activation by the replication initiator Cdc6.
Nat Commun, 12:3883-3883, 2021
Cited by
PubMed Abstract: The Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. The S. cerevisiae ORC binds to specific DNA sequences throughout the cell cycle but becomes active only when it binds to the replication initiator Cdc6. It has been unclear at the molecular level how Cdc6 activates ORC, converting it to an active recruiter of the Mcm2-7 hexamer, the core of the replicative helicase. Here we report the cryo-EM structure at 3.3 Å resolution of the yeast ORC-Cdc6 bound to an 85-bp ARS1 origin DNA. The structure reveals that Cdc6 contributes to origin DNA recognition via its winged helix domain (WHD) and its initiator-specific motif. Cdc6 binding rearranges a short α-helix in the Orc1 AAA+ domain and the Orc2 WHD, leading to the activation of the Cdc6 ATPase and the formation of the three sites for the recruitment of Mcm2-7, none of which are present in ORC alone. The results illuminate the molecular mechanism of a critical biochemical step in the licensing of eukaryotic replication origins.
PubMed: 34162887
DOI: 10.1038/s41467-021-24199-1
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.6 Å)
Structure validation

237735

数据于2025-06-18公开中

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