Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation

Nat Struct Mol Biol. 2016 Mar;23(3):217-24. doi: 10.1038/nsmb.3170. Epub 2016 Feb 8.

Abstract

The CMG helicase is composed of Cdc45, Mcm2-7 and GINS. Here we report the structure of the Saccharomyces cerevisiae CMG, determined by cryo-EM at a resolution of 3.7-4.8 Å. The structure reveals that GINS and Cdc45 scaffold the N tier of the helicase while enabling motion of the AAA+ C tier. CMG exists in two alternating conformations, compact and extended, thus suggesting that the helicase moves like an inchworm. The N-terminal regions of Mcm2-7, braced by Cdc45-GINS, form a rigid platform upon which the AAA+ C domains make longitudinal motions, nodding up and down like an oil-rig pumpjack attached to a stable platform. The Mcm ring is remodeled in CMG relative to the inactive Mcm2-7 double hexamer. The Mcm5 winged-helix domain is inserted into the central channel, thus blocking entry of double-stranded DNA and supporting a steric-exclusion DNA-unwinding model.

Publication types

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

MeSH terms

  • Cryoelectron Microscopy
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism*
  • DNA Helicases / ultrastructure*
  • DNA Replication*
  • Models, Molecular
  • Protein Conformation
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / enzymology*

Substances

  • DNA Helicases