5DGO

Crystal structure of cell division cycle protein 45 (Cdc45)

Summary for 5DGO

• Entry DOI: 10.2210/pdb5dgo/pdb
• Descriptor: Cell division control protein 45 homolog, 1,2-ETHANEDIOL, SULFATE ION, ... (4 entities in total)
• Functional Keywords: dna replication, cmg helicase subunit, recj fold, cell cycle
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: O75419
• Total number of polymer chains: 1
• Total formula weight: 64937.61

Authors

Simon, A.C.,Pellegrini, L. (deposition date: 2015-08-28, release date: 2016-05-25, Last modification date: 2024-11-13)

Primary citation

Simon, A.C.,Sannino, V.,Costanzo, V.,Pellegrini, L.
Structure of human Cdc45 and implications for CMG helicase function.
Nat Commun, 7:11638-11638, 2016

PubMed Abstract: Cell division cycle protein 45 (Cdc45) is required for DNA synthesis during genome duplication, as a component of the Cdc45-MCM-GINS (CMG) helicase. Despite its essential biological function, its biochemical role in DNA replication has remained elusive. Here we report the 2.1-Å crystal structure of human Cdc45, which confirms its evolutionary link with the bacterial RecJ nuclease and reveals several unexpected features that underpin its function in eukaryotic DNA replication. These include a long-range interaction between N- and C-terminal DHH domains, blocking access to the DNA-binding groove of its RecJ-like fold, and a helical insertion in its N-terminal DHH domain, which appears poised for replisome interactions. In combination with available electron microscopy data, we validate by mutational analysis the mechanism of Cdc45 association with the MCM ring and GINS co-activator, critical for CMG assembly. These findings provide an indispensable molecular basis to rationalize the essential role of Cdc45 in genomic duplication.

PubMed: 27189187
DOI: 10.1038/ncomms11638

Experimental method

X-RAY DIFFRACTION (2.1 Å)