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

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

Author information

1
Department of Biochemistry &Cell Biology, Stony Brook University, Stony Brook, New York, USA.
2
Biology Department, Brookhaven National Laboratory, Upton, New York, USA.
3
DNA Replication Laboratory, Rockefeller University, New York, New York, USA.
4
Howard Hughes Medical Institute, Rockefeller University, New York, New York, USA.
5
Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, Texas, USA.

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.

PMID:
26854665
PMCID:
PMC4812828
DOI:
10.1038/nsmb.3170
[Indexed for MEDLINE]
Free PMC Article

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