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

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.

SUBMITTER: Yuan Z

PROVIDER: S-EPMC4812828 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Yuan Zuanning Z Bai Lin L Sun Jingchuan J Georgescu Roxana R Liu Jun J O'Donnell Michael E ME Li Huilin H

Nature structural & molecular biology 20160208 3

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 upo ...[more]

PMID: 26854665

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DNA unwinding mechanism of a eukaryotic replicative CMG helicase.

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