6XTY

CryoEM structure of human CMG bound to AND-1 (CMGA)

Summary for 6XTY

• Entry DOI: 10.2210/pdb6xty/pdb
• Related: 5OGS
• EMDB information: 10619 10621
• Descriptor: DNA replication licensing factor MCM2, DNA replication complex GINS protein SLD5, Cell division control protein 45 homolog, ... (13 entities in total)
• Functional Keywords: cmg, helicase, atpase, replisome, replication
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 14
• Total formula weight: 1104143.57

Authors

Rzechorzek, N.J.,Pellegrini, L.,Chirgadze, D.Y.,Hardwick, S.W. (deposition date: 2020-01-16, release date: 2020-05-27, Last modification date: 2024-09-25)

Primary citation

Rzechorzek, N.J.,Hardwick, S.W.,Jatikusumo, V.A.,Chirgadze, D.Y.,Pellegrini, L.
CryoEM structures of human CMG-ATP gamma S-DNA and CMG-AND-1 complexes.
Nucleic Acids Res., 48:6980-6995, 2020

PubMed Abstract: DNA unwinding in eukaryotic replication is performed by the Cdc45-MCM-GINS (CMG) helicase. Although the CMG architecture has been elucidated, its mechanism of DNA unwinding and replisome interactions remain poorly understood. Here we report the cryoEM structure at 3.3 Å of human CMG bound to fork DNA and the ATP-analogue ATPγS. Eleven nucleotides of single-stranded (ss) DNA are bound within the C-tier of MCM2-7 AAA+ ATPase domains. All MCM subunits contact DNA, from MCM2 at the 5'-end to MCM5 at the 3'-end of the DNA spiral, but only MCM6, 4, 7 and 3 make a full set of interactions. DNA binding correlates with nucleotide occupancy: five MCM subunits are bound to either ATPγS or ADP, whereas the apo MCM2-5 interface remains open. We further report the cryoEM structure of human CMG bound to the replisome hub AND-1 (CMGA). The AND-1 trimer uses one β-propeller domain of its trimerisation region to dock onto the side of the helicase assembly formed by Cdc45 and GINS. In the resulting CMGA architecture, the AND-1 trimer is closely positioned to the fork DNA while its CIP (Ctf4-interacting peptide)-binding helical domains remain available to recruit partner proteins.

PubMed: 32453425
DOI: 10.1093/nar/gkaa429

Experimental method

ELECTRON MICROSCOPY (6.77 Å)