PDBsum entry 5dgo

Cell cycle

PDB id: 5dgo

Contents

Protein chain

541 a.a.

Ligands

EDO ×6

SO4 ×3

Waters ×541

PDB id:

5dgo

Name:

Cell cycle

Title:

Crystal structure of cell division cycle protein 45 (cdc45)

Structure:

Cell division control protein 45 homolog. Chain: a. Synonym: porc-pi-1. Engineered: yes. Other_details: residues 154 to 164 (11 aminoacids) were left out of the expression construct used for determination of the crystal structure.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdc45, cdc45l, cdc45l2, unq374/pro710. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: rosetta 2.

Resolution:

2.10Å R-factor: 0.169 R-free: 0.195

Authors:

A.C.Simon,L.Pellegrini

Key ref:

A.C.Simon et al. (2016). Structure of human Cdc45 and implications for CMG helicase function. Nat Commun, 7, 11638. PubMed id: 27189187 DOI: 10.1038/ncomms11638

Date:

28-Aug-15 Release date: 25-May-16

Protein chain

O75419  (CDC45_HUMAN) -  Cell division control protein 45 homolog from Homo sapiens

Seq: 566 a.a.

Struc: 541 a.a.

DOI no: 10.1038/ncomms11638

Nat Commun 7:11638 (2016)

PubMed id: 27189187

Structure of human Cdc45 and implications for CMG helicase function.

A.C.Simon, V.Sannino, V.Costanzo, L.Pellegrini.

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.