Structure of the eukaryotic MCM complex at 3.8 Å

Nature. 2015 Aug 13;524(7564):186-91. doi: 10.1038/nature14685. Epub 2015 Jul 29.


DNA replication in eukaryotes is strictly regulated by several mechanisms. A central step in this replication is the assembly of the heterohexameric minichromosome maintenance (MCM2-7) helicase complex at replication origins during G1 phase as an inactive double hexamer. Here, using cryo-electron microscopy, we report a near-atomic structure of the MCM2-7 double hexamer purified from yeast G1 chromatin. Our structure shows that two single hexamers, arranged in a tilted and twisted fashion through interdigitated amino-terminal domain interactions, form a kinked central channel. Four constricted rings consisting of conserved interior β-hairpins from the two single hexamers create a narrow passageway that tightly fits duplex DNA. This narrow passageway, reinforced by the offset of the two single hexamers at the double hexamer interface, is flanked by two pairs of gate-forming subunits, MCM2 and MCM5. These unusual features of the twisted and tilted single hexamers suggest a concerted mechanism for the melting of origin DNA that requires structural deformation of the intervening DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / ultrastructure
  • Chromatin / chemistry
  • Conserved Sequence
  • Cryoelectron Microscopy*
  • DNA / chemistry
  • DNA / metabolism
  • DNA / ultrastructure
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / ultrastructure
  • G1 Phase
  • Minichromosome Maintenance Proteins / chemistry*
  • Minichromosome Maintenance Proteins / metabolism
  • Minichromosome Maintenance Proteins / ultrastructure*
  • Models, Biological
  • Models, Molecular
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / ultrastructure
  • Nucleic Acid Denaturation
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry*
  • Protein Subunits / metabolism
  • Replication Origin
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae / ultrastructure*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / ultrastructure


  • Cell Cycle Proteins
  • Chromatin
  • MCM5 protein, S cerevisiae
  • Multienzyme Complexes
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • DNA
  • DNA synthesome
  • DNA-Directed DNA Polymerase
  • MCM2 protein, S cerevisiae
  • Minichromosome Maintenance Proteins

Associated data

  • PDB/3JA8