Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer

Nat Struct Mol Biol. 2017 Mar;24(3):300-308. doi: 10.1038/nsmb.3374. Epub 2017 Feb 13.


The minichromosome maintenance complex (MCM) hexameric complex (Mcm2-7) forms the core of the eukaryotic replicative helicase. During G1 phase, two Cdt1-Mcm2-7 heptamers are loaded onto each replication origin by the origin-recognition complex (ORC) and Cdc6 to form an inactive MCM double hexamer (DH), but the detailed loading mechanism remains unclear. Here we examine the structures of the yeast MCM hexamer and Cdt1-MCM heptamer from Saccharomyces cerevisiae. Both complexes form left-handed coil structures with a 10-15-Å gap between Mcm5 and Mcm2, and a central channel that is occluded by the C-terminal domain winged-helix motif of Mcm5. Cdt1 wraps around the N-terminal regions of Mcm2, Mcm6 and Mcm4 to stabilize the whole complex. The intrinsic coiled structures of the precursors provide insights into the DH formation, and suggest a spring-action model for the MCM during the initial origin melting and the subsequent DNA unwinding.

MeSH terms

  • Adenylyl Imidodiphosphate / chemistry
  • Amino Acid Motifs
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / ultrastructure
  • Cryoelectron Microscopy
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / ultrastructure
  • Minichromosome Maintenance Proteins / chemistry*
  • Minichromosome Maintenance Proteins / metabolism
  • Minichromosome Maintenance Proteins / ultrastructure
  • Models, Molecular
  • Protein Domains
  • Protein Multimerization*
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / ultrastructure
  • Zinc Fingers


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • TAH11 protein, S cerevisiae
  • Adenylyl Imidodiphosphate
  • Minichromosome Maintenance Proteins