The structural basis for MCM2-7 helicase activation by GINS and Cdc45

Nat Struct Mol Biol. 2011 Apr;18(4):471-7. doi: 10.1038/nsmb.2004. Epub 2011 Mar 6.


Two central steps for initiating eukaryotic DNA replication involve loading of the Mcm2-7 helicase onto double-stranded DNA and its activation by GINS-Cdc45. To better understand these events, we determined the structures of Mcm2-7 and the CMG complex by using single-particle electron microscopy. Mcm2-7 adopts two conformations--a lock-washer-shaped spiral state and a planar, gapped-ring form--in which Mcm2 and Mcm5 flank a breach in the helicase perimeter. GINS and Cdc45 bridge this gap, forming a topologically closed assembly with a large interior channel; nucleotide binding further seals off the discontinuity between Mcm2 and Mcm5, partitioning the channel into two smaller pores. Together, our data help explain how GINS and Cdc45 activate Mcm2-7, indicate that Mcm2-7 loading may be assisted by a natural predisposition of the hexamer to form open rings, and suggest a mechanism by which the CMG complex assists DNA strand separation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Enzyme Activation
  • Minichromosome Maintenance Proteins
  • Models, Molecular
  • Protein Conformation


  • Cdc45 protein, Drosophila
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Drosophila Proteins
  • MCM2 protein, Drosophila
  • Minichromosome Maintenance Proteins